Department of Clinical Physiology, Nuclear Medicine & PET

Annual Report 2016

Rigshospitalet · University of Copenhagen Contents

Preface...... 2 Mission and objectives...... 4 Organisation and staff 2016...... 6 Highlights 2016...... 10 Medical secretaries...... 13 “Sundhedsplatformen”...... 15 Clinical physiology and nuclear medicine, KF Section...... 17 Clinical physiology and nuclear medicine, Glostrup Section ...... 18 Rigshospitalet Paediatric Nuclear Medicine...... 20 King Frederik V founded Rigshospitalet in 1757. Today it has app. 1,400 beds and 12,000 employees. Cardiac 82Rb-PET/CT...... 22 Research at Rigshospitalet is published in more than 2,000 peer review papers per year, including Education...... 25 higher academic theses (PhD and Doctor of Medical Science). Rigshospitalet is part of The Capital Nuclear medicine technologists, radiographers and lab technicians...... 27 Region of Denmark and is a Copenhagen University Hospital. Cyclotron Section...... 30 Radiochemistry Section...... 34 Glostrup Hospital New PET/CT scanner Glostrup...... 38 Glostrup Hospital were established in 1958, and 1st of January 2015 Rigshospitalet, Blegdamsvej and PET/CT...... 40 Glostrup Hospital were unified as Rigshospitalet. PET scanning of the brain...... 42 PET/MR...... 44 University of Copenhagen MR imaging of the brain...... 46 The University of Copenhagen was founded in 1479. The Faculty of Health and Medical Sciences has PET and PET hybrid systems...... 48 10,000 students, including medicine and bioengineering in collaboration with The Technical University Equipment 2016 ...... 50 of Denmark, DTU. The University of Copenhagen is member of IARU, the International Alliance of Academic and other activities...... 52 Research Universities and LERU, League of the European Research Universities. www.ku.dk Studies ...... 56 Finance...... 59 Publications...... 60 Research...... 68 Cluster for Molecular Imaging...... 76 Collaboration with Landssygehuset, Faroe Islands...... 80 CIMBI...... 82 MSc in Medicine and Technology...... 84 Danish National Research Foundation...... 86 Accreditation...... 88 Preface

The research in our department has reached unpresidented with a trauma center level 1. Due to good collaboration and old Rigshospitalet), and the section in Glostrup. It was a big effort, Thank you to our directors at the Center of Diagnostics, hights in 2016 with a new uPAR tracer from Professor Andreas a great effort and resilience from all it is now onboard. Thank well prepared and with a good collaboration with Carestream and Rigshospitalet, Center Director Bettina Lundgren, MD DMSc Kjær, who is at the helmet as responsible for research at the you to all our staff members for the great dedication and the CIMT, Susanne Thomassen. A warm thank you also to our own and Vice Director Lene Ørnstrup and their team for important department. Andreas has an ERC Advanced Grant, and we are effort. Our consultant in PET, Dr Johan Löfgren was responsi- experts Annegrethe Jørgensen, Bryan Haddock, Peter Hovind, Lis positive and helpful collaboration. Thank you to Department of privileged to house his comprehensive program of molecular ble for the operation in our department, and we would like to Larsen, Katrine Cappelen, Maria Pejtersen, Marianne Stahlfest, Radiology, Head of Department Ilse Vejborg and Chief Radio- imaging. We are proud of the uPAR PET tracer developed for convey a warm thank you to Johan for the successful effort. Tina Vikmann Nielsen, Gudrun Semitoje and Vibeke Rønn. grapher Johnny Madelung. We appreciate the positive collabo- grading invasiveness and malignancy in PET/CT scanning. To Also a warm thank you to our “super users” Head of Section, ration very much. all other researchers in the department: also a warm thank you Consultant Peter Hovind, Consultant Peter Oturai and all other The unification between Glostrup and Rigshospitalet is now in and honors for your fine effort. employees involved. During the “go live” period we got great place, and works well with teleconference facilities and integra- Thank you to all staff, collaborators and international colleagues help from “The Student Team” formed under the leadership of tion on patient studies, research and education. for making this possible. To all experts and staff members a warm thank you for a busy Bioengineer Student David Kovacs, previous president of the year with high standards and the implementation of “Sundheds- student organization “Engineering World Health”. David and his The highlight of the year was the introduction of the new PET/CT Our aim is to deliver the best patient treatment and the best platformen”, the new electronic patient record. The acitivity in 35 student colleagues were second to none during the “go live” scanner in Glostrup; the first PET/CT in Glostrup. We would research and education. 2016 was very high with a busy clinical everyday practice with period, worked 24/7 and were essential for the success of the like to say a warm thank you to Head of Section, Consultant >111,000 investigations. implementation. We would like to say a warm thank you to all Peter Hovind, Staff Nuclear Medicine Technologist Lis Larsen students involved. and Physicist Bryan Haddock, Glostrup and the team in PET, In 2016 Rigshospitalet implemented the new electonic patient Blegdamsvej, Head of Section, Consultant Annika Loft, Consult- record, the EPIC SP, “Sundhedsplatformen”. Preparations with Before we could implement the new electronic patient record ant Anne Kiil Berthelsen and Staff Nuclear Medicine Technologist education and training started before the summer, and on the we had to upgrade the patient booking system Carestream RIS Kate Pedersen for helping the Glostrup Section. Our idea was, 5th of November 2016 when we had “go live”. Rigshospitalet in our section in Glostrup, so that we had the same all over that PET in all our sections should have the same quality – the Liselotte Højgaard Linda M. Kragh has 12,700 employees, and is the only hospital in Denmark Rigshospitalet, both on the premises in town, Blegdamsvej (the highest obtainable – for the sake of patients and research. Professor, Head of Department Chief Technologist

2 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 3 Mission and objectives

The mission and objectives of the Department of Clinical Physiology, Nuclear Medicine & PET are:

33 to provide optimal clinical physiology and nuclear medicine for patient investigations and patient treatment with radiopharmaceuticals 33 to carry out research at the highest international level in clinical physiology and nuclear medicine with special emphasis on molecular imaging, isotopes and radiopharmaceuticals 33 to deliver undergraduate and postgraduate education for all relevant professionals nationally and internationally 33 to provide a good patient experience with emphasis on quality and patient security and ensure wellbeing of patients, relatives and staff.

We aim high – we strive to be one of the five best departments worldwide before 2020.

4 department of clinical physiology, nuclear medicine & pet Organisation and staff 2016 Department of Clinical Physiology, Nuclear Medicine & PET

Head of Department, Chief Nuclear Professor, MD, Medicine Abrahamsson, Elisabeth, Radiographer. Cappelen, Katrine Louise, Engineer. Edem, Patricia Edim, MSc Chem., PhD, Postdoc. DMSc Technologist Liselotte Højgaard Linda Kragh Aggergaard, Amalie, Student. Chehri, Sarah, Scholarship. Elkington, Sakeena, NMT. Agner, Elissaveta Castella, Radiographer. Choudry, Aisha Bilal, Student. Ellebæk, Sofie, MSc Biotech., PhD Student. Ahmadi, Amir, Radiographer. Christensen, Anders, MD, PhD Student. Ellegaard, Andreas Høyby, Student. Albers, Mia C. Hjorth, Teaching NMT. Christensen, Camilla, Chemist. Enevoldsen, Lotte Hahn, MD, Consultant. Chief Physicist Professor, Consultant, MD, Albrecht-Beste, Elisabeth, MD, Consultant. Christensen, Camilla, NMT. Engberg, Astrid, Student. Thomas Levin DMSc, PhD, MBA Klausen Alslev, Louise, MD, Staff Specialist. Christensen, Charlotte Birk, MD, Staff Specialist. Eschen, Christian, Student. Andreas Kjær Al-Tai, Reya Tarik Hamid, NMT. Christensen, Esben, MSc Bio Med, PhD Student. Esmail, Mona Jasmin Ali, NMT. Amtoft, Annemarie Gjelstrup, MD, Consultant. Christensen, Helle, NMT and Nurse. Federspiel, Marianne, NMT. Anderberg, Lasse, Student. Christensen, Jan Damgaard, Cyclotron Technician. Fischer, Barbara Malene, MD, DMSc, PhD, Consultant. Head Medical Andersen, Flemming Littrup, MSc, PhD, Chief Christensen, Kirstine Kjær, Student. Fliedner, Frederikke Petrine, MSc Biotech., PhD Student. Secretary Computer Scientist. Christensen, Line-Marie Neumann, Student. Foldager, Annette, Teaching NMT. Vibeke Rønn Andersen, Julie Bjerglund, MD, PhD, Registrar. Christensen, Thomas Emil, MD, PhD Student. Folkmann, Nanna Freja, Secretary. Andersen, Kim Francis, MD, Consultant. Christensen, Tine Nøhr, MD, PhD Student. Fosbøl, Marie Øbro, MD, PhD Student. Andersen, Ulrik Bjørn, MD, Consultant. Christophersen, Daniel Vest, MSc Human Biology, Frederiksen, Mette, Quality Coordinator. Anthony, Erwin Jørry, Cyclotron Technician. PhD, Postdoc. Frost, Nadia, Student. Awwal, Zara Amalie Krog, Radiographer. Clausen, Malene Martini, MD, PhD, Postdoc. Frydendahl, Christina Schjøth, MSc Chem, PhD, Glostrup Section KF Section WholebodyCounter PET Section Cyclotron Radiochemistry Azizi, Nadia, Radiographer. Clemmensen, Andreas Ettrup, MSc Med.Tech., Postdoc. Section Section Barløse, Mads Christian Johannes, MD, Registrar. PhD Student. Fuchs, Annette, Student. Bay, Emma Therese, Student. Cortsen, Annette, NMT. Gelle, Liibaan Mohamed, NMT. Section Head, Chief Beich, Laura Tange, Student. Costa, Junia, MD, Staff Specialist. Ghotbi, Adam Ali, MD, PhD Student. Section Head, Section Head, Cyclotron Chief, Consultant, MD, Cyclotron Chief, Radiochemist , Bentsen, Simon, PhD Student. Cramer, Stig Præstekjær, MD, PhD, Postdoc. Gillings, Nic, MSc, PhD, Chief Radiochemist. Consultant Consultant MSc, PhD PhD MSc, PhD Production Peter Hovind Jann Mortensen Holger Jensen Annika Loft Holger Jensen Manager Benzon, Eric von, MD, Consultant. Dahan, Daniel, Cyclotron Technician. Ginsborg, Lone Agervold, Medical Secretary. Jakobsen Jacob Madsen Berthelsen, Anne Kiil, MD, Consultant. Dall, Bente, NMT. Grave, Tine, Medical Secretary. Beyer, Birgit Krindel, Staff Technologist. Dalsgaard, Birthe Hunnerup, NMT. Grøndahl, Veronica Lykke, Scholarship. Staff Staff Consultant Staff Assistant Chief Binderup, Tina, MSc Human Biology, PhD, Postdoc. Damgaard, Jeannette, Radiographer. Gudmundsdóttir, Edda Rós, NMT. Technologist Technologist Technologist Cyclotron Chief Radiochemist Birch, Kirsten Junker, NMT. Damm, Kristina, Secretary. Gutt, Lars Emil, Student. LisLarsen Birgit Krindel Peter Oturai Kate Pedersen Jesper Jørgensen NicGillings Beyder Bisgaard, Sissel, Student. de Nijs, Robin, Medical Physicist, MSc, PDEng, PhD. Haddock, Bryan Thomas, Chief Physicist. Borgwardt, Lise, MD, PhD, Consultant. Dejanovic, Danijela, MD, Staff Specialist. Hag, Anne Mette Fisker, MSc Human Biology, PhD, Brandt-Larsen, Malene, MSc, PhD, Chemist. Denholt, Charlotte Lund, MSc, PhD, Chemist. Postdoc, Research Coordinator. Chief NMT Staff Technologist Brittain, Jane Maestri, MD, Senior Registrar. Do, Manh Tan, Student. Hansen, Adam Espe, Physicist. Linda M. Kragh Buhelt, Sophie, Student. Drachmann, Anders Paaske, Student. Hansen, Anders Elias, DVM, PhD, Postdoc. Anne Sørensen Bærentsen, Christian Ørtoft, Student. Dunbar, Douglas, NMT. Hansen, Anja Vallin, NMT, Clinical Instructor. Børresen, Betina, DVM, PhD Student. Dähnhardt, Andreas, System Administrator. Hansen, Camilla Josephine Teglgaard, NMT. Calvo, Oriol Puig, PhD Student. Døssing, Kristina Benedikte Vangsted, MSc Biology, Hansen, Caroline Lind Hansen, NMT. Cappelen, Anna, Student. PhD Student. Hansen, Casper, Student.

6 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 7 Organisation and Staff 2016

Hansen, Christian Engelsborg, Student. Jensen, Michael Lundemann, Engineer. Krogager, Louise, Student. Magnusson, Linda Helena Margaretha, Technologist. Pedersen, Maria Badir, Student. Setterberg, Victoria, NMT. Hansen, Christian, Student. Jensen, Vibeke, NMT. Kronvall, Johanna, NMT. Malmberg, Catarina Anna Evelina, MD, Scholarship. Pedersen, Sune Folke, MSc Human Biology, PhD, Simonsen, Helle Juhl, NMT. Hansen, Helena, Student. Jeppesen, Troels Elmer, MSc Chem, PhD Student. Ladefoged, Claes Nøhr, Computer Scientist, Marner, Lisbeth, MD, DMSc, PhD, Staff Specialist. Postdoc. Skou, Katrine Bugge, MSc Med.Tech, Research Hansen, Joachim Pries, Student. Johannesen, Helle Hjorth, MD, Consultant. PhD Student. Martín, Marina Simón, Student. Pejtersen, Maria, NMT. Assistant. Hansen, Matilde Bro, Student. Johannesson, Rasmus Skov, Student. Langer, Jonathan Andreas Wang, Student. Mehlsen, Anne-Birgitte, MD, Consultant. Petersen, Lars Ringgaard, MSc Bio.Med., PhD Skovgaard, Dorthe Charlotte, MD, PhD, Postdoc. Hansen, Michele Zaugg, Student. Johansen, Shakti Nicolai, NMT. Langer, Natasha Hemicke, Student. Mikkelsen, Henny, NMT. Student. Sommer, Niyan, NMT. Hansen, Ole Michael Raun, NMT. Johnbeck, Camilla Bardram, MD, PhD, Postdoc. Larsen, Anne Fensløv, Student. Mikkelsen, Mathias, Student. Petersen, Lotte Pia, Service Assistant. Stahlfest, Marianne, Medical Secretary. Hasbak, Philip, MD, Consultant. Juhl, Karina, MSc Human Biology, PhD Student. Larsen, Bjarke Follin, MSc Ind.Med., PhD Student. Mohebbi, Ali, Student. Philipsen, Frederik Ersø, Student. Stahr, Karin, NMT. Hasler, Signe Walther, Student. Jørgensen, Annegrethe, NMT. Larsen, Christina Vang, NMT. Morsing, Anni, MD, Consultant. Porojan, Monica, Technician. Strandberg, Sandra, Student. Hassan, Mariam, NMT. Jørgensen, David, Student. Larsen, Lis, Staff Technologist. Mortensen, Jann, MD, DMSc, Consultant, Poulsen, Constance Eline Grandjean, Student. Suetta, Charlotte Arneboe, MD, PhD, Consultant, Hassing, Christina, Student. Jørgensen, Jennifer Solgaard, MSc Engineer Larsen, Mette Fabiansen, Medical Secretary. Ass. Professor. Poulsen, Jákup Martin, Radiographer. Ass. Professor. Henriksen, Otto Mølby, MD, PhD, Consultant. Biotech., PhD Student. Larsen, Trine Bjørnbo, MSc Pharm Tech, Mose, Camilla, NMT. Poulsen, Sidsel Højklint. Sunde, Christine Høj, NMT. Hercman, Alexandra Regina Nowacka, NMT. Jørgensen, Jesper Tranekjær, MSc Human Biology, PhD Student. Mottelson, Mathis Nygaard, Student. Pourhassan, Houman, MSc Bio.Chem., PhD Student. Svalling, Susanne, NMT. Hildebrand, Sanne, Secretary. PhD, Postdoc. Larsson, Henrik Bo Wiberg, MD, DMSc, Consultant, Munkholm-Larsen, Mathias, Clinical Assistant. Raghava, Jayachandra Mitta, MSc Biology, Postdoc. Svendsen, Nini Hvidtfeldt, NMT. Hirsi, Abdi Hafied, Registrar. Jørgensen, Jesper, MSc, Cyclotron Physicist. Professor. Myltoft, Mette Gylling, Medical Secretary. Rahbek, Rikke Sofie, Student. Sørensen, Anne, Staff Technologist. Holm, Stine, NMT. Jørgensen, Louise, MD, Research Assistant. Lass, Jakob, Student. Myschetzky, Rebecca Sue Main, NMT. Rasmussen, Camilla Kuhre, Medical Secretary. Sørensen, Jette Bitten, Service Assistant. Holm, Søren, MSc, PhD, Chief Physicist. Jørgensen, Mads Wissenberg, Registrar. Laugesen, Monika, Student. Mølvig, Bjørn Hübschmann, Student. Rasmussen, Gregers Brünnich Damgaard, MD, Sørensen, Louise Lendorf Sørup, NMT. Holten, Victoria, Student. Jørgensen, Mette Møller, NMT. Law, Ian, MD, PhD, Consultant, Professor. Nielsen, Anders Bo, Student. PhD Student. Tayyab, Mahvish, NMT. Holtz, Simon Herken, MSc Molecular Biology, Kaijer, Michelle Westergaard, Technologist, Lehel, Szabolcs, MSc Chemistry, PhD. Nielsen, Carsten Haagen, MSc Med.Tech., PhD, Rasmussen, Sine Hvid, Student. Teksen, Alime Sema, Student. QA Academic. PA Professor Andreas Kjær. Lind, Camilla Louise Nordvig, NMT. Postdoc. Rasmussen,Thomas, MD, PhD, Postdoc. Therkildsen, Pia, Secretary. Hovind, Peter, MD, DMSc, Consultant. Karnov, Kirstine, MD, PhD Student. Lindberg, Ulrich, MSc Med.Tech, PhD. Nielsen, Cora Schaumann, NMT. Reichkendler, Michala, MD, Senior Registrar. Tolstrup, Britt Maria Jæger, Radiographer. Hurry, Preetee Kapisha, MD, Senior Registrar. Keller, Sune Høgild, MSc, PhD, Computer Scientist. Lindell, Elin, NMT. Nielsen, Kasper With, Animal Technologist. Rexhepi, Lume, NMT. Vestergaard, Mark Bitsch, PhD Student. Højgaard, Liselotte, MD, DMSc, Professor, Kjær, Andreas, MD, DMSc, PhD, MBA, Consultant, Linnet, Simone, Student. Nielsen, Mariane, Service Assistant. Ripa, Rasmus Sejersten, MD, DMSc, Staff Specialist. Vignisdottir, Lilja Dögg, Radiographer. Head of Department. Professor. Linnet, Solveig, NMT. Nielsen, Tina Vikmann, Medical Secretary. Risør, Louise Madeleine, MD, PhD Student. Vinther, Johanne Constance Ilve, Management Iljazovska, Cejlan Zulfovska, NMT. Kjær, Kristian Skov, Student. Ljunggren, Anna, NMT. Nyrnberg, David Enslev, Student. Rosiek, Christian Anker, Student. Secretary. Ismaili Abd, Scholarship. Klausen, Thomas Levin, MSc, Chief Physicist. Loft, Mathias Dyberg, Scholarship. Nørgaard, Martin, Engineer. Rostrup, Egill, MD, DMSc, Consultant. Weihrauch, Per, Cyclotron Technician. Jakobsen, Annika Loft, MD, PhD, Consultant. Kleczewski, Karina, Medical Secretary. Ludvig, Helle, NMT. Nørregaard, Kamilla, MSc Physicist, PhD, Postdoc. Ruager, Martin Siim, Student. Wikke, Tina, NMT. Jakobsen, Mette Høy, Human Biology, PhD Student. Knigge, Pauline Natalie Seindal, Student. Lundberg, Helena Inez Sofia, MD, Registrar. Nørst, Tim Niclas, NMT. Rønbirk, Lilian, Medical Secretary. Wittekind, Anne-Mette Nielsen, QA Pharmacist. Jensen, Berit, NMT. Knudsen, Camilla Sloth, NMT. Lundby, Tim Mølgaard, Staff Technologist. Olesen, Oline Vinter, MSc Engineer, PhD. Rønn, Vibeke, Head Medical Secretary, PA Professor Wrang, Helene, NMT. Jensen, Holger, MSc, PhD, Chief Cyclotron Physicist. Knudsen, Lisbet Lomholdt, Consultant. Lundsgaard, Christoffer Cramer, Student. Olin, Anders. Student. Liselotte Højgaard. Yerst, Joo Lærke, NMT. Jensen, Julie Milbak, Student. Korsholm, Kirsten, MD, Senior Registrar. Lærke, Sonja Pedersen, Technician. Olsen, Ingrid Marie Holst, MD, PhD, Postdoc. Rønne, Frederik Malmborg, MD, Senior Registrar. Yousaf, Roma Urooj, Student. Jensen, Mads Radmer, Registrar. Kragh, Linda M., Chief Technologist. Löfgren, Johan, MD, Consultant. Olsen, Paw Winther, Engineer. Salihu, Armend, NMT. Østergaard, Daniella Elisabet, Student. Jensen, Martin Juul Ravn, NMT. Krarup, Marie Manon Krebs, Scholarship. Madsen, Casper Lillegård, Student. Oturai, Peter, MD, Consultant. Saxtoft, Eunice, NMT, Clinical Instructor. Aagaard, Christina Byrne Faurholt, MD, PhD Student. Jensen, Mathilde Daniele Ørbæk, Scholarship. Kristensen, Lotte Kellemann, MSc Human Biology, Madsen, Jacob, MSc, PhD, Chemist, Chief Oxbøl, Jytte, Technologist, Lab. Manager. Schulze, Christina, NMT. Jensen, Mette Munk, MSc Human Biology, PhD, PhD Student. Production Manager. Pedersen, Kate, Staff Technologist. Segur, Liva, Student. Postdoc. Kristiansen, Jonas Frimer, Student. Madsen, Lasse Ahlbech, Student. Pedersen, Kirsten Foldberg, Radiographer. Semitoje, Gudrun, Medical Secretary.

8 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 9 Professor Andreas Kjær got the JNM Editors Choice Award for the best article at Highlights 2016 the Society of Nuclear Medicine Annual SUNDHEDS PLATFORMEN Meeting: “64Cu-DOTATATE PET for Neuroendocrine Tumours: A Prospective New electronic patient record, Head-to-Head “Sundhedsplatformen” at Rigshospitalet. Comparison with Our Head of 111In-DTPA-Octreotide Department, Professor in 112 Patients”. Liselotte Højgaard was invited by the Swedish Chief Technologist Linda M. Government to join the Board Kragh got the speciality’s prize (Konsistoriet) of the Karolinska Institute as the first non-academic at the in Stockholm. The Karolinska Insitute is DSKFNM’s Annual Meeting. one of the leading medical universities New staff room and hands out the Nobel Prizes in the KF Section 2016. physiology or medicine.

Professor Liselotte Højgaard was invited to join the Board of Die Robert Bosch Stiftung who owns 92 % of Robert Bosch GMBH, a world wide company with an annual return of 70 billion € and 350,000 employees. The foundation owns Rigshospitalet is at the company and Die Robert Bosch Krankenhaus the moment building in Stuttgart, a hospital like Rigshospitalet, and the a new North Wing, foundation supports research, art, humanities and a 2 bio project, and in humanitarian actions all over the world. 2016 the constructions The staff survived with have necessitated that the a little sunshine in an Annual Education Conference for all staff PET Section was covered by intermistic pavilion. members in Department of Clinical Physiology, a heavy lid of concrete. Nuclear Medicine & PET.

10 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 11 Medical secretaries

In the department we have highly competent medi- work load. A dedicated thank you to Tina Vikmann cal secretaries important for referral of patients, Nielsen, Gudrun Semitoje, Mette Gylling Myltoft, organisation of the flow of patients through the Lilian Rønbirk, Lone Agervold Ginsborg, Marianne department, writing the reports and sending them Stahlfest, Mette Fabiansen Larsen, Kristina Damm, to the clinical departments. They do a dedicated Camilla Kuhre Rasmussen, Nanna Folkmann and effort , and we have no waiting lists for patients Pia Therkildsen. or reports. In all three sections we have been challenged by staff members who have been ill Our Head Medical Secretary Vibeke Rønn is for longer periods, but in spite of that the teams assistant to the management of the department and have performed brilliantly. The medical secretaries also a great help in the daily work, when needed. master the complicated booking and secure that We would like to say a warm thank you to every- the waiting lists, the patient control examinations one for the high quality and performance. and research scans can be done in spite of a high

department of clinical physiology, nuclear medicine & pet 13 “Sundhedsplatformen”

Johan Löfgren

After more than two years of preparations of health care professionals. Rigshospitalet was the In order to secure the success of the project, “Sundhedsplatformen” - a new hospital informa- second hospital in line to take on this challenge. Student in Engineer in Medicine & Technology tion system was implemented at Herlev/Gentofte At our department we use RIS/PACS (Radiology David Kovacs organized the “Diagnostic Center Hospital in May 2016 as the first hospital in Den- Information System and Picture Archiving and Student Team”, a team with 36 dedicated and mark. Sundhedsplatformen a modern Electronic Communication System) for registration and docu- intelligent students. After initial training they Medical Record (EMR) software delivered by Epic mentation of data including images. RIS/PACS have since “Go-live” been at the hospital day and will be implemented at all hospitals in Region was not to be replaced by Sundhedsplatformen. night to assist physicians and other staff mem- Hovedstaden and Region Sjælland over the next Instead integrations between the two systems bers to manage and overcome hurdles within years. Sundhedsplatformen replaces many prior should fulfil the clinical needs allowing our staff Sundhedssplatformen. Their help has been highly IT-systems and gather all relevant information to work mainly in RIS/PACS and clinicians to appreciated and their initial 4 weeks’ support has and data in one platform which enables easy work in Sundhedsplatformen. been extended to at least the double. chart overview, advanced decision support and statistical functionality. The vision is to optimize Software training of our staff started in Sep- For our department this EMR change has only the quality and enhance the effectivity for the tember and “Go-live” of Sundhedsplatformen meant minor change in our daily work, but for the benefit of patients and health care professionals - at Rigshospitalet took place on the 5th of Novem- clinicians it has caused a real paradigm shift in Sundhedsplatformen will make it easier to be ber 2016. Even though a lot of small obstacles their way of working. Just 6 weeks after “Go-live” patient and easier to be a health care professional. emerged, the implementation went rather we can conclude that in some areas it looks promi- smooth. One of the greatest challenges has been sing and health care professionals have adapted Changing an EMR involves a lot of preparations, the integrations to other IT-systems, especially to the new workflows, but in other areas there is still including large configuration work, workflow the clinical laboratory information system a long way to go before Sundhedsplatformen harmonization and software training of the (LABKA) but also to our RIS/PACS. can be summarized as a success story.

14 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 15 Clinical physiology and nuclear medicine The KF Section

Jann Mortensen and Peter Oturai

The KF Section at Blegdamsvej offers a variety of Treatment with 223Radium (223Ra) was initiated specific for NET diagnostics is a central function nuclear medicine and clinical physiological exa- in Denmark at Rigshospitalet in May 2014. Until for the care of the patients at the NET-Center. minations. Among these are PET/CT for cardiac the end of 2016 the department has given 575 Patients from Odense University Hospital, Aarhus (82Rb), neuroendocrine (68Ga-DOTATOC), paedia- 223Ra treatments to 157 patients with castration University Hospital and abroad are referred to us tric (18F-FDG) diseases, lung (ventilation/perfusion resistant prostate cancer and symptomatic bone for 177Lu-DOTATATE treatment. The NET-Center SPECT/CT; mucociliary clearance scintigraphy; metastases. The treatment is given to outpatients at Rigshospitalet has been accredited as Center of lung physiology measurements), and oncological from all over the country as an intravenous in- Excellence by the European Neuroendocrine Tu- (sentinel node scintigraphy; bone SPECT/CT; jection typically every four weeks for a total of mour Society (eNETS). MUGA) investigations. Other frequent investiga- six planned series. Since 223Ra is an alpha-emitter tions are SPECT/CT and scintigraphy for various extra safety handling procedures are needed to 177Lu-DOTATATE - synthesized and labelled at the endocrine disorders, renography and DMSA-scin- protect the staff involved in the direct handling Hevesy Laboratory at Risø, DTU, and is admini- tigraphy for nephro-urologic diseases, DXA-scan for and administration. These procedures include stered in our facilities - binds to neuroendocrine bone mineral density and whole body composition, whole body counter measurements to ensure no tumours expressing somatostatin receptors. Beta- and 51Cr-EDTA-clearance for GFR measurement. internal contamination to the staff. particles from the 177Lu-isotope destroy the tumour cells and the gamma photons are used for scinti- To provide these state-of-the-art nuclear medicine Since 2009 treatment with 177Lu-DOTATATE to graphic imaging and dosimetry. investigations to most clinical departments in the patients with neuroendocrine tumours (NET) hospital, the department makes use of: 1 PET/CT has been performed in the department. Until the For many years the department has successfully scanner, 3 hybrid SPECT/CT cameras, 1 dual-head end of 2016, 188 patients have been given a total treated patients with benign thyroid diseases – gamma camera, 4 single-head cameras, 2 Jaeger of 681 treatments. We are an active part of the goitre and hyperthyroidism – with 131I-iodine. body plethysmographs and 1 DXA-scanner. All the NET-Center at Rigshospitalet working in close In 2016 we have had weekly and monthly con- equipment is extensively used for both routine pa- collaboration with the Departments of Gastro ferences dealing with neuroendocrine tumours, tients and for research investigations. Diagnostic Surgery, Oncology, Radiology, Pathology and En- thyroid diseases, paediatric oncology, cardiology, ultrasound is used as an adjunct to thyroid scinti- docrinology at Rigshospitalet. Our performance and lung, adrenal and orthodontic diseases. graphy in patients having thyroid diseases. of more than 550 68Ga-DOTATOC-PET/CT scans

department of clinical physiology, nuclear medicine & pet 17 Clinical physiology and nuclear medicine The Glostrup Section

Peter Hovind

In the Glostrup Section we have a long tradition Using the tilt test examination under standard- multicenter study collecting a Danish reference of combining classical clinical physiology with ized situations with our 2 Task Force tilt test material which was completed this year. modern nuclear medicine methods. monitors, we examine patients with dizziness, episodes of falling and syncope episodes. We can We have 3 DXA-scanners, 2 Lunar Prodigy scan- Our section examines patients hospitalized at the measure blood pressure on the extremities, where ners and 1 Lunar iDXA scanner. The two Prodigy Glostrup location of Rigshospitalet, patients from blood pressure in the lower limbs can be evalu- scanners are mainly used for the measurement of Glostrup outpatient clinic, as well as patients ated in patients with claudication or ulcers, as bone mineral density in patients with or suspected from general practice in the surrounding area. well as equipment for measurement of systemic for osteoporosis. The Lunar iDXA scanner is at blood pressure over 24 hours for detection and present exclusively used for research purposes Parallel to the new possibilities, we continue to evaluation of hypertension in adults and children. with respect to musculoskeletal research, led by perform routine nuclear medicine imaging and We assist in diagnosing secondary hypertension Associate Clinical Research Professor Charlotte with our 3 dedicated gamma SPECT/CT cam- with Captopril renography, Doppler ultrasound Suetta, who is studying the plasticity of skeletal eras and 2 single head gamma cameras. One of renal arteries and analysis of urinary steroid muscle in respond to ageing, inactivation and of the latter has just been replaced with a new metabolism, and receive patients from the Capital various disease states by combining whole muscle NephroCam for kidney examinations. In addition, Region and Region Zealand. function with DXA, fMRI, PET/MR, molecular we perform many different types of planar and signaling and stem cell analyses. Within the last SPECT/CT examinations. This includes DAT-scan- In patients with stroke, we examine the arteries three years, we have established a Danish refe- ning which visualize dopamine transport receptor to the brain for plaques and eventual stenoses of rence material consisting of 1,400 healthy controls binding in the brain for diagnosing Parkinson’s the vessels. Diagnostic ultrasound is also used to- for body composition, bone mineral density in disease and other neurological diseases involving gether with thyroid scintigraphy in patients with parallel with muscle strength and physical perfor- dopamine transport receptors. Other examples disease in the thyroid. mance in collaboration with the Copenhagen City are bone scintigraphy for rheumatologic diseases Heart study. Within the next year we are planning and evaluation of surgery performed in the spine For measuring of lung function, we have a Jaeger to move further with these assessments of muscle with various prosthesis, as well as renography for body pletysmograph where patients with COPD, mass and function in various patient groups. At kidney diseases and follow-up on kidney function asthma and preoperative lung testing are present the research group consists of 2 PhD stu- in patients with spinal cord injury. performed. We participated as a part of a large dents and 4 graduate students.

18 department of clinical physiology, nuclear medicine & pet Paediatric Nuclear Medicine

Lise Borgwardt

In 2016 we performed more than 3,000 paediatric In our children section we have a children-friendly Our Glostrup Section is specialized in detection nuclear medicine investigations. It is a special focus PET/128SliceCT, a SPECT/CT, an EDTA Clearance and evaluation of hypertension in children with area for our department to perform these investiga- and a renography room. PET/MR-scans are per- equipment for measurement of systemic blood tions at the highest level of excellence, and at the formed in the PET Section. In each scanner room pressure over 24 hours and assist in the assess- same time make it a positive experience for both in the children section, high quality projectors are ment for secondary hypertension in children with the child and its parents. The department is a mem- showing films at the ceiling to secure and entertain Doppler ultrasound of renal arteries, receiving ber of the EANM Paediatric Committee and the the child during the scan. In the waiting area the patients from the Capital Region and the Region Paediatric Imaging Harmonization SNM/EANM. children have the opportunity to watch the ani- Zealand. mated decorations, use apps or watch films at the Our experience is, that PET/MR can solve real tablets giving when entering the section or play Research in paediatric nuclear medicine and PET life clinical diagnostic dilemmas and PET/MR in the toy corner. We offer 20 specially produced is necessary, as we have an increasing amount of is indeed a technique that can be used robustly films and audio essays: “20 stories for the children medical doctors, PhD students and technicians in clinical practice. We find the combination of of Rigshospitalet”, both films for projection on the involved in the field and we conduct research regional PET/MR and WB PET/CT on the same ceiling and audios essays to listen to while walk- protocols in children with PET/MRI in order to tracer injection especially useful, since we get ing around looking at the wall decoration during develop this interesting area, but also methods the hybrid scan information with high soft tissue tracer uptake period, that make our children have for evaluating regional liver function in children. discrimination from PET/MR and the good hybrid less sedation and feel entertained and secure while staging scan with the highest diagnostic value of visiting our department. The work in the EANM Paediatric Committee this the lung parenchyma from PET/CT and it all in year has been very interesting and inspiring, and an acceptable timeframe. Also our clinicians are Our multidisciplinary paediatric haematology we are looking forward to next year’s work as very impressed by this combination of modalities. and oncology conferences are presented as a web vice chair in the committee. based nuclear medical platform combined with In 2016 we continued participating in randomized videoconference including districts outside the clinical trials for experimental immunotherapy for capital. Our collaborators are very pleased with children with cancer as a part of the Nordic Center the possibilities and the advantages in the diag- for these treatments. nostic evaluation of the children.

20 department of clinical physiology, nuclear medicine & pet Cardiac 82Rb-PET/CT

Philip Hasbak

Rigshospitalet was the first hospital in Scandi- function is an important domain of cardiac 82Rb- Cardiac and renal 123I-MIBG scintigraphy navia and one of the first in Europe to diagnose PET. Traditionally, cardiac PET images have been In 2010 we introduced cardiac 123I-metaiodoben- ischemic heart disease using cardiac 82Rb-PET/CT visually interpreted, using uptake as a measure zylguanidine (123I-MIBG). Radiotracer analogues as a new type of advanced imaging system. of function. This approach, however, takes only a of the sympathetic mediator norepinephrine fraction of the full PET information into account. have been investigated extensively and are at the At Rigshospitalet there is a special need to The application of tracer kinetic modelling to brink of potential widespread clinical use, espe- provide cardiac PET every day, since a large dynamically measured data is able to extract cially after the presentation of the ADVANCE-HF proportion of our patients with ischemic heart objective measures of perfusion and/or meta- trial. The most widely studied SPECT tracer, disease need an acute or sub-acute work-up that bolism, depending on the tracer. While such true 123I-MIBG has consistently shown a strong, in- requires quick decision making as to coronary cardiac quantification has been troublesome and dependent ability to risk stratify patients with revascularization strategy. Patients with unstable time-consuming in the past, our new cardiac advanced congestive heart failure. Recently we angina or non-STEMI should be revascularized tools now makes this state-of-the-art technology have evaluated 123I-MIBG as an estimate of renal with percutaneous coronary intervention (PCI) readily available. Further, we offer CT coronary sympathetic nervous activity. within 3 days after admission or with coronary angiography (CTCA) which is useful for planning artery bypass graft surgery (CABG) within 5-7 many invasive cardiac procedures, particularly Research-wise we have a close and good coopera- days according to The Danish National Board of complex PCI procedures including chronic total tion with various clinical departments. Health. Non-invasive assessment of myocardial occlusions (CTOs) and bifurcation stenting.

22 department of clinical physiology, nuclear medicine & pet Education

Jann Mortensen, Peter Oturai & Peter Hovind

All together the facilities at the KF Section and Colleagues and students from Denmark and the Glostrup Section comprize seven educational abroad, have visited the department for educa- positions for young physicians training to become tional and research purposes for periods ranging specialists in clinical physiology and nuclear medi- from weeks to months. cine. Other roles in the specialist education of physicians are related to the dedicated courses in The department delivers training programmes oncology-, cardiology-, pulmonology-, endocrino- to staff from other nuclear medicine and radio- logy- and pathophysiology as well as more basic logical departments in Denmark and the Nordic courses in methodology (MR and kinetics), all held countries. at our department and arranged by our professors and consultants. Furthermore, we contribute to The departments educational activities have been the specialist education of physicians from other accredited by the Accreditation of Nuclear Medi- specialities such as urology, nephrology, radiology, cine Training Centres Committee of the Section of oncology, haematology, pulmonology and thoracic Nuclear Medicine of the European Union of Medical surgery. A high number of PhD students are associ- Specialists (UEMS) and The Danish Health ated with the research activities in the department. Authorities.

Regarding undergraduate education, nuclear Consultant Peter Oturai and Consultant Peter medicine technologist students and radiographer Hovind are responsible for the postgraduate students receive part of their education at the education of physicians in the department. As- department. The department contributes to the sociate Professor Jann Mortensen and Professor activities of the Faculty of Health Sciences at the Henrik Larsson are responsible for the under- University of Copenhagen for Medical students, graduate education of medical students in the Human Biology students and Medicine & Tech- department. Professor Liselotte Højgaard is nology students in collaboration with DTU in vari- responsible for under- and postgraduate educa- ous subjects, e.g. physiology, nuclear medicine, tion for bioengineers. and medical technology.

department of clinical physiology, nuclear medicine & pet 25 Nuclear medicine technologists, radiographers and lab technicians

Kate Pedersen, Anne Sørensen, Birgit Krindel Beyer og Lis Larsen

Nuclear medicine technologists, radiographers and a renovation of the radiochemistry laboratories gists and radiographers from Blegdamsvej have lab technicians have also this year participated in and a tough autumn with absent colleagues due been working in Glostrup to secure the same high post graduate education, meetings and congresses, to maternity leave and disease. level everywhere in our department. It is very along with busy everyday life with an increasing positive to see how the experienced staff mem- number of patient investigations and participation bers have collaborated with those learning the in research projects together with education of new PET technique; it has been a very positive many groups. All of it with the highest quality and experience for all. It has increased the knowledge a positive attitude to the many different tasks. The about our two different sections, the PET Section group of radiographers are now 9 in total, and a and the Glostrup Section, and the collaboration union represensative has been elected. All partici- between them has worked very nicely. Thank you pate in securing a good working environment in to Staff Nuclear Medicine Technologist Lis Larsen, the sections, and it is a privilege to lead the group. the Glostrup Section and Staff Nuclear Medicine Technologist Kate Pedersen, the PET Section for In June 2016 the KF Section welcomed the new the fine planning and support. Staff Nuclear Medicine Technologist Birgit Krindel Beyer. Birgit has more than 20 years of experience In the summer in clinical physiology and nuclear medicine. Birgit October 2016 a PET/CT-scanner was installed in 2016 the Glostrup has just finished the leadership education program Glostrup. Three nuclear medicine technologists Section finalized at the Capital Region of Copenhagen this fall and from Glostrup were in training in the PET Section the large project as our new leader we are all very enthusiastic for at Blegdamsvej to assure readiness for imple- on population her abilities and her open, professional and posi- mentation of the scanner. In the month following based studies tive attitude to all tasks and everyday life. nuclear medicine technologists and radiographers on muscular Nuclear Medicine Technologist Tina Wikke and from the PET Section at Blegdamsvej have been strength and lab technician Sonja Pedersen Lærke have opti- in Glostrup to assist in the learning period. Maria DEXA investiga- mized and process validated a method for pro- Pejtersen started the first six weeks and Bente Dall tions. Almost 1,500 volunteers from the general duction of 68Ga-PSMA for the diagnosis of pros- has helped with the PET brain scans. Following public were DEXA scanned, had impedance and tate cancer. This was done simultaneously with this the well trained nuclear medicine technolo- muscular strength measurements performed.

department of clinical physiology, nuclear medicine & pet 27 Nuclear medicine technologists, radiographers and lab technicians

One of the focus areas at the KF Section this year Physical exercise has been to optimize the working conditions and Of course we the booking schedule at our PET/CT scanner. It participate in the is used for various studies: 82Rb rest/stress myo- annual DHL. cardial scans with cardiac CT, 18F-FDG myocardial metabolism, 68Ga-DOTATOC scans diagnosing neuroendocrine tumours and 18F-FDG scans pri- marily on children. Nuclear Medicine Technologist Elin Lindell past the A typical day at the scanner starts at 7 A.M. with clinicial instructor education with the project: “Port- quality control of the 82Rh generator and starting folio – How can it be used as an educational tool?” up the scanner. After injection the first patient is scanned at 8.15 A.M. The daily program consists As Nuclear Medicine Technologist Douglas Dun- of a mix of the mentioned investigations, and 6-9 bar says: “When I have made a balloon animal, Annual meeting DSKFNM (Danish Society of patients are examined every day. Logistically it is they don’t see me as the guy in the white uni- Clinical Physiology and Nuclear Medicine) a challenge to ensure a flow that secures that the form, but the guy with the balloon animals and Linda Kragh and Mia Hjorth Albers gave a talk PET/CT scanner is in use all day, and we have it is an ice breaker moving the kids concern and about clinical instructors in our department. therefore expanded the daily staffing from 2 to 3 the investigation can be performed quietly”. nuclear medicine technologists/radiographers. In addition we have introduced monthly meetings with physicians, physicists, secretaries, nuclear Working environment medicine technologists and radiographers to en- The PET Section have had a tough year with roof sure that logistics is continuously optimized. over the open atrium due to building the new North Wing. All the offices and staff rooms have The paediatric task force in our department has been in the dark. After a great effort with econo- participated in a balloon course for nuclear med- my and bureaucracy we succeeded in having icine technologists and radiographers with the “daylight” light in all rooms, and it has been an im- Presentations at EANM in Barcelona Presentation at the International MR meeting Presentation at SNM in USA aim of learning how to make balloon animals for provement for the very day working life. There are Poster from Mette Møller Jørgensen, Søren Holm in Singapore Poster from Marianne Federspiel, Karin Stahr, children referred to paediatric nuclear medicine several arrangements to secure a good working life Linda M. Kragh, our Chief Nuclear Medicine & Jann Mortensen. Posters from Helle Juhl Simonsen. Adam Espe Hansen, Liselotte Højgaard and investigations. Now we can make professional in the sections; in the PET Section a PET party and Technologist and part of the leadership of our Poster from Eunice Saxtoft and Kirsten Junker Birch Andreas Kjær. balloon animals like in the circus and it has given in the KF Section creativity afternoons with knit- department, got the speciality’s prize as the first Poster from Bente Dall, Christina Schulze, good results and improved the childrens percep- ting, homemade cookies and nice conversation, non-academic and with a very honourable speech Camilla Sloth Knudsen and Anna Ljunggren tion of our complicated scanning investigations. including both the department and private life. from the president of the society. – they got the third place for their poster.

28 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 29 Cyclotron Section

Figure 1. Development in total number of productions, 18F and 11C productions since 2006.

Holger J. Jensen and Jesper Jørgensen Figure 2. Average received doses per year for employees in the Cyclotron- and Radiochemistry During the last years we have experienced a sta- 33 A new system for loading and unloading the unit since 2006. ble number of productions at our two cyclotrons 81Rb target was developed and the control of approximately 1,200 productions per year, see system was programmed in our new Siemens figure 1. In 2016 we had in total 1,180 successful Simatic S7 PLC SCADA system. productions (532 and 648 for our Scanditronix MC32 and Siemens RDS Eclipse cyclotrons re- 33 A new helium cooling system for the 81Rb spectively) and only 1 cancelled production. As in target was designed and build this year. The the previous years we also managed to keep the control system will be integrated in the exis- average radiation dose to the employees in the ting cyclotron SCADA system in early 2017. Cyclotron- and Radiochemistry Section at a low The cooling system is designed for 8 targets in level, see figure 2. total and will be used for future new targets planned to be build and mounted at the com- Examples of ongoing and/or finished upgrade ing new beamline-2 system. The work on the projects for our Scanditronix MC32 cyclotron: new beamline 2 is planned to start late 2017.

33 The new target for production of 81Rb for our 33 The upgrade of the electronics in the RF sys- Rb/Kr generators, designed and built last tem (RLC, RPM, RDRC and RDRA) described year, was taken into successful use this year. in previous annual reports was finalized this The target was replacing the 24 year old origi- year by purchasing a complete new spare nal target. RLDC unit form the company AXCON Aps. Figure 3. The new RLDC unit from Axon Aps.

30 department of clinical physiology, nuclear medicine & pet Cyclotron Section

Chimney Filter bunker

Figure 5. Visualization of chimney and building for filter units.

Figure 4. The new home made 11C target.

The most important development for our production, which were initiated in 2011 and Siemens/CTI RDS Eclipse cyclotron this year was planned to be finished in 2016, had to be rede- the development of a new 11C target. The goal of signed this year due to major financial problems. the new target is to improve both target yields In the new design the chimney has been moved and specific activities. In addition to this it is the from the original position at the house end of hope to be able to produce [11C]-Methane in the “Centralkomplekset” to a position close to the en- target. In the standard 11C target design from trance from Blegdamsvej, see figure 5. CTI/Siemens only the less interesting [11C]- Carbondioxide can be produced. The testing A partly underground bunker for all filter units is and validation is ongoing. planned to be built at the same corner. The pro- ject is expected to be finished October 2017. The project, described in previous annual reports, for building a new chimney for release of radio- active gases produced in our radiopharmacy

32 department of clinical physiology, nuclear medicine & pet Radiochemistry Section

Nic Gillings and Jacob Madsen

Highlights radiochemical yields compared with the old system. Radiopharmaceutical development This has enabled us to reduce the number of 33 The first human studies using our in-house productions by around 10 % whilst still meeting Neurology developed angiogenesis imaging agent, [68Ga] demand. Following a phase I clinical trial in A dopamine transporter ligand, [18F]FE-PE2I, 68 Ga-NODAGA-cRGDyK2 started in November 2015 to evaluate the uPAR imaging agent [ Ga] which is used for studying patients with Par- 2016. Ga-NOTA-AE105, five new phase II clinical trials kinson’s disease was set up and validated in 33 2 new PET-tracers, [18F]FE-PE2I and [68Ga] were commenced in 2016. For angiogenesis ima- 2016 and an application for human use was Ga-PSMA-HBEC-CC were validated in 2016. ging, a Phase I clinical trial with [68Ga]Ga-NODA- submitted in December. For Alzheimer’s disease

Applications to the Danish Medicines Agency GA-cRGDyK2 commenced in November 2016. imaging, production of a new PET tracer for for clinical use were submitted at the end of 11 different radiopharmaceuticals were produced imaging tau proteins is being implemented, and the year. for human use in 2016 (see Figure). an application for human use is expected to be 33 In 2016 one of our GMP radiochemistry pro- submitted in 2017. duction laboratories was refurbished including In order to keep up with regulatory requirements installation of 5 new hotcells. for good manufacturing practice (GMP), one of Oncology our production laboratories was completely reno- The prostate cancer imaging agent, [68Ga]Ga- vated in 2016, including installation of 5 new PSMA-HBED-CC was validated in 2016 and an Production for clinical and research PET hotcells and a new dispensing system. Along with application for human use was submitted at the investigations in humans complying with GMP, this will also increase our end of the year. The production of [18F]ASIS Production of [18F]FDG and [81m]Krypton gene- capacity to introduce new tracers for human use. (active site-inhibited factor VIIa) for human use rators along with [18F]FET, [18F]FLT, [68Ga] is currently being validated and a clinical trial Ga-DOTATOC and [11C]PIB continued a similar Production of neuroreceptor PET tracers for application will be submitted in 2017. Several level compared to 2015. From February 2016 we human use, for various research projects con- other tracers targeting biological processes related moved totally over to the GE FASTlab synthesis ducted by the Neurobiology Research Unit at to cancer are available for preclinical investiga- platform for [18F]FDG production. This system Rigshospitalet continued at a similar level to tions, for example [18F]ApoPep-1 for imaging of minimizes the risk of failures and gives higher previous years. apoptosis and [18F]HX-4 for hypoxia imaging.

34 department of clinical physiology, nuclear medicine & pet Radiochemistry Section Radiopharmaceutical Batches Produced Usage/Target 7 [18F]FDG 312 Oncology/Glucose metabolism Radiopharmaceuticals produced for human use in 2016 [68Ga]Ga-DOTATOC 250 Neuroendocrine tumours/Somatostatin receptors Krypton-81m generator 151 Lung ventilation [11C]PIB 106 Alzheimer’s Disease/β-amyloid plaques [18F]FET 84 Oncology/amino acid transport [18F]FLT 11 Oncology/cell proliferation tracer [68Ga]Ga-NOTA-AE105 52 Oncology/uPAR imaging [15O]Water 12 Cerebral blood flow 11 35 [ C]AZ10419369 Brain Research/5-HT1B receptors 11 [ C]SB207145 47 Brain Research/5-HT4 receptors 11 [ C]Cimbi-36 6 Brain Research/5-HT2A receptors 68 [ Ga]Ga-NODAGA-cRGDyK2 2 Oncology/angiogenesis imaging

Neurobiology ASIS (active site-inhibited factor VIIa) using 5-HT7 receptor. Furthermore, Fraser Edgar started Abdallah Omar A Abdelmawjoud started a mas- Our collaboration with the Neurobiology Research fluorine-18 and copper-64. a master’s project in May 2016 aimed at devel- ter’s project in September 2016 aimed at the de- Unit, Rigshospitalet and the Department of Drug oping phenylpiperazine based PET tracers, for velopment of new fluorine-18 labelled derivatives

Design and Pharmacology, Faculty of Health and The promising results obtained with our 5-HT2A 5-HT7 receptors imaging. The 5-HT7 receptor is of ligands targeting uPAR. Medical Sciences, University of Copenhagen con- PET ligand, [11C]Cimbi-36, encouraged us to involved in many brain disorders such as depres- tinued as in previous years. Development and try to develop a fluorine-18 labelled analogue. sion and currently no validated PET tracer exists. evaluation of new PET tracers for a number of In her PhD project, Ida Nymann Petersen has Education in radiopharmaceutical chemistry targets was undertaken in 2016. Among these are labelled a number of analogues using various Johanna Steen continued her PhD project in 2016 A new teaching program in radiopharmaceutical [11C]Martinostat for imaging histone deacetylase labelling strategies and these have been evalu- focussed on carbon-11 and fluorine-18 labelled chemistry led by Associate Professor Matthias (HDAC) and various analogues for imaging phos- ated in animals. Ida will submit her PhD thesis click agents for pre-targeted imaging. This ap- Herth was initiated in spring 2016 at the Faculty phodiesterase type 1 (PDE1). Several other new in early 2017. proach can potentially allow imaging of long- of Health and Medical Sciences, University of tracers are currently in the pipe-line. circulating nanostructures with short-lived isotopes. Copenhagen. 7 students successfully passed the Elina Nyberg L’ Estrade started her PhD project in Also, Patricia Edem started a postdoc position in theoretical and practical exams. Several of these January 2016. She will develop combinatorial- April 2016. She will work in the same field, have decided to continue as master students

Radiopharmaceutical research and PhD projects like fluorine-18 labelling approaches for 5-HT7 developing PET tracers for pre-targeted imaging within the field of radiopharmaceutical science. Troels Elmer Jeppesen continued his PhD project selective ligands, which will ultimately result of internalised targets. Lara Ali and Placid Orji, searching for new protein radiolabelling strate- in easy access to a broad variety of derivatives. who started master’s projects in September 2016, gies. In particular the project is focused on radio- These will be used to screen and identify effi- will also work on the development of pre-targeted labelling chemically modified derivatives of ciently the best tracer candidates for imaging the imaging agents.

department of clinical physiology, nuclear medicine & pet 37 New PET/CT scanner Glostrup

Peter Hovind

For a long period of time, the Glostrup Section where Physicist Bryan Haddock lead a building was one of the few places in the entire country, project to create our sections PET facility in just where PET/CT were not a part of the armamen- two months with lot of assistance from the expe- tarium of examinations offered. As part of a rienced staff in the PET Section at Blegdamsvej. larger department with extended possibilities Just three months after signing the contract with of collaboration accross geographical localities, a Siemens, the first patient scan was performed new PET/CT-scanner became a more viable invest- and a close and successful collaboration between ment than ever. In December 2015 the department the section at Blegdamsvej and the section in management made acquiring the PET/CT for the Glostrup has ensued. Three days a week whole- Glostrup Section its top priority. Late February body scans are preformed and the remaining 2016, the news came that the funds for the scan- two days we perform dedicated brain scans with ner were granted after which the bidding process regular rotations of doctors and technicians be- concluded with the purchase of a new Siemens tween the two sections in a fruitful collaboration Biograph mCT. After the contract was signed at ensuring high quality of PET/CT examinations at the end of June, a rather quick process ensued our section.

38 department of clinical physiology, nuclear medicine & pet PET/CT

Annika Loft Jakobsen and Anne Kiil Berthelsen

In oncology and in infectious and inflammatory One of our new focus areas is the implementa- diseases the use of FDG PET/CT is increasing tre- tion of PET/CT in multidisciplinary team confe- mendously around the world – and we have been rences or tumour boards participating in almost part of this from the very beginning! We now 20 every week. Another important issue is testing perform more than 10,000 PET/CT scans per new tracers and investigating the clinical indica- year. The trend in oncology treatment is persona- tions for these. lized medicine and PET/CT plays a natural role in this new paradigm. In 2016 we have been fortunate to be able to expand our scanner park - now we have 6 whole- With clinical research imbedded in our everyday body PET/CT scanners with the newest scanner work, we have had the opportunity to take part placed in new surroundings at our Glostrup Sec- in many clinical trials with results that now are tion with important logistic challenges to solve in implemented in our clinical routine, e.g. deep an inspiring collaboration with new colleagues. inspiration breathhold PET/CT for radiotherapy planning of malignant lymphoma and the use of PET/CT for gynaecological cancers.

40 department of clinical physiology, nuclear medicine & pet PET scanning of the brain

Otto Mølby Henriksen and Ian Law

1 The overall goal of the neuro-PET group is to Tyrosine (FET), the somatostatin II receptor ligand Figure 1. Example of multi-modality PET/MRI charac- continuously improve use of PET and hybrid [Ga68]-DOTATOC, and [C11]-PiB. FET has an terization performed in a 7 year old boy with an imaging in routine clinical brain imaging and to established role in the management of brain tu- incidentally found lesion in the right basal ganglia further explore hybrid imaging of brain physiology mour, and is increasingly been evaluated using area. Within a single 40 minute session dynamic in both the diseased and healthy brain. PET/MR. We are in the process of developing [F18] Flouro-Ethyl-Tyrosine (FET) PET, standard structural MRI and various advanced MRI sequences FET PET/MR as a multiparametric tool in pae- were obtained. Post-contrast T1 (CE T1) and T2 FLAIR The Siemens hybrid PET/MR scanner has been diatric neurooncology. An example is shown in showed a solitary contrast-enhancing lesion without implemented into clinical routine investigations Figure 1. By a close collaboration with anesthesi- edema. Diffusion weighted imaging did not show re- for dementia. The diagnostic package consist- ologists, simultaneous PET and MR assessment of duced ADC and thus not indicative of increased cellu- ing of 4-5 standard MR sequences focused at disease is available also to smaller children, and larity and MR spectroscopy (MRS) demonstrated only localizing structural and vascular pathology are thereby reduces the stress of repeated anesthesia moderately increased choline, which is considered a combined with primarily FDG in a short and otherwise required in this sensitive population. marker of malignancy. Perfusion MRI (DSC BV) did very comprehensive one-stop imaging shop for not show increased blood volume. Dynamic FET PET dementia. An automated hippocampus volume- For radiotherapy planning and the evaluation found moderately increased uptake with an increasing tric report now adds to the assessment of patients of recurrent meningioma we are employing time-activity curve. Based on the combined imaging a with early stages of neurodegenerative disease. [Ga68]-DOTATOC using our high resolution re- differentiation of a neoplasm from inflammatory (or other non-neoplastic) pathology could not be made, Our experience is that PET/MR can solve real search tomograph (HRRT) PET scanner, as the but it was concluded that a high grade glioma or life clinical diagnostic dilemmas and PET/MR is growth pattern of meningioma, and the small other aggressive malignancy was unlikely. Follow-up indeed a technique that can be used robustly in margins of the stereotactic radiation therapy MRI after 3 months showed regression of contrast en- clinical practice. In a single 15 min. session a pa- used make a 2 mm resolution desirable. [C11]- hancement pointing towards a demyelinating lesion. tient may receive a thorough and comprehensive PiB amyloid binds to amyloid plaques, a patho- [Figure reproduced from Marner et al., Clinical and structural and function neuroimaging examina- logical hallmark for Alzheimer's disease and is Translational Imaging, in press] tion of outstanding image quality. used to support the diagnosis.

Our non-FDG radiotracers have had a relative Collaborating with international and clinical science projects explore the use of the most re- increase in the overall production. They consist research partners and the Functional Imaging cent development in radiopharmaceuticals and of the amino acid analogue [F18] Flouro-Ethyl- Unit at Glostrup, a number of clinical and basic MR imaging.

42 department of clinical physiology, nuclear medicine & pet 7 Figure 2: PET/MRI examination of a 72 year old male with a metastatic gastrooesophageal junction cancer. The patient is scanned on a prototype flat table top in PET/MR a project evaluating the use of PET/MRI in target defi- nition in radiotherapy treatment of spinal metastases. Sagittal PET/MR images (from left, anatomic MRI (T1 TSE), fused PET/MRI and PET) show a metastatic transformed S1- and S2-segment (arrow) which affects both S1- and S2-nerve roots

7 Figure 3.PET/MRI examination of a patient with head/ neck squamous cell carcinoma. The voxel wise relation of the Apparent Diffusion Coefficient (ADC) and FDG uptake (right) was studied in an anatomically defined region of interest (yellow contour). A cluster analysis of the tumour heterogeneity carried out in combined parameter space. Reference: J Rasmussen et al, Journal of Nuclear Medicine (online December 2016)

Johan Löfgren and Adam Espe Hansen

The integrated PET/MRI system offers a unique The experience and expertise gained through cancer and chronic multifocal osteomyelitis in Current research directions include the analysis combination of functional and molecular imaging PET/MRI research studies has helped to identify children. of multi-modality functional imaging data as with state-of-the-art anatomic imaging. These capa- relevant clinical applications. The main areas of shown in Figure 3, here with combined FDG-PET bilities are being exploited in clinical, translational clinical PET/MRI at the department are neurolo- To take full advantage of the PET/MRI multi- and diffusion weighted MRI. Other current re- and basic research, as well as for clinical exami- gy, neuro-oncology and paediatric oncology. modality imaging combination a few technical search topics include atherosclerosis, neurobiol- nations. Since installation, the number of clinical Here the PET/MRI provides a time-efficient and challenges have had to be addressed. At the de- ogy and the combination of PET and hyperpolar- examinations performed has been growing steadily. logistically advantageous examination for pa- partment we have early pointed to the issue of ized MRI. We have at the end of 2016, 25 active tients with all relevant imaging being obtained attenuation correction, in particular of the brain. research protocols. in a single scanning session. For children an A multi-center study led by the department, which additional advantage is reduction of radiation included the evaluation of in-house developed exposure compared to traditional PET/CT where methods, has recently concluded that this issue CT normally accounts for 2/3 of the total radia- can be considered solved. Imaging for RT planning tion dose. The most frequent clinical indication requires attenuation correction of the RT flat table is dementia (see section on PET scanning of the top, which has been implemented for the pro- brain). Examples of other indications currently ject shown in Figure 2. Another methodological under investigation at the department, where accomplishment has been the demonstration of PET/MRI appears promising include RT planning simultaneous PET and hyperpolarized Carbon-13 Figure 1: The number of PET/MR examinations per year of head/neck cancer and spine metastases (Fig- based MR spectroscopic imaging, which has been since installation is shown ure 2), response evaluation of lung and cardia investigated in phantoms and in animals.

44 department of clinical physiology, nuclear medicine & pet MR imaging of the brain

Henrik Larsson

7 Functional Imaging Unit (FIU) is involved in in one session before and after injection of Dia- Figure 1. SPECT perfusion scan using the basic neuro-physiological research and develop- mox, using Arterial Spin Labelling (ASL), a fast radioactive tracer 99mTc-HPMAO before and after ment of new diagnostic methods. As an example, and non-invasive method. Figure 1 and figure injection of Diamox of a 75 year old patient with we have during the last couple of years, together 2 shows SPECT and MRI ASL scans before and severe right internal carotid artery stenosis. The with Department of Neurology developed a test after Diamox administration, respectively. We right sided diminished perfusion is easily seen battery allowing us to obtain detailed informa- generally find a high degree of concordance be- with no increase after Diamox. tion about the vascular system in patients with tween the two kinds of measurement. The versa- small and large brain vessel diseases, of rele- tile MRI allows measurements of other important 7 Figure 2. MRI perfusion scan using Arterial Spin vance in diseases as stroke, Mb Binswanger (sub- metrics, as absolute total brain flow through Labelling before and after Diamox of the same cortical leucoencephalopathy or small vessel vas- the basilar and internal carotid arteries and the patient and same slice as presented in Figure 1. cular dementia) and Alzheimer’s disease where brains total oxygen consumption. Incorporating As in Figure 1, the asymmetric perfusion pattern vascular insufficiency likely augment disease a Dynamic Contrast Enhanced (DCE) MRI gives can be seen. progression. The so-called cerebral vascular re- information about capillary mean transit time serve capacity (CVR), i.e. the ability of the brain and transit time heterogeneity and blood brain 7 vessels to dilate and increase perfusion, is impor- barrier permeability. Figure 3 shows DCE MRI Figure 3. The figures show results of the Dynamic tant to secure a sustained oxygen delivery to the measurements of the same patient as in the pre- Contrast Enhanced MRI of the same subject as brain. Traditionally, the CVR is measured by per- vious figures. in the above figures after injection of Diamox. Perfusion (CBF) is asymmetrically decreased in forming a SPECT scan before and after injection the right hemisphere; the Mean Transit Time of acetazolamide (Diamox – acting as a vasodila- These physiological images can be compared (MTT) is prolonged and the Capillary Transit 99m tor) using the radioactive tracer Tc-HMPAO. to structural MRI images, such as white matter Time Heterogeinity (CTH) is increased in the lesions, infarctions, and local brain atrophy, and right hemisphere including deep grey matter. The new test employs Magnetic Resonance provides detailed information about the well-being Interpretation of CTH is currently an active area of Imaging (MRI), where perfusion is measured of the brain. research, especially in relation to oxygen transport.

46 department of clinical physiology, nuclear medicine & pet PET and PET hybrid systems

Thomas Levin Klausen and Søren Holm

In 2016 we installed one new PET/CT scanner tic quality CT including contrast enhancement. than PET/CT, but also has the potential of in the Glostrup Section, and the department One of the mCT's is run in a unique well-func- reducing radiation exposure, which is particularly now has 1 dedicated, stand-alone brain PET system, tioning collaboration with the Department of Ra- important in childrens examination. The physics 6 combined whole-body PET/CT systems and 1 diotherapy, and it is extensively used for therapy group has been working on the issues of attenua- integrated PET/MR system. planning, for which purpose its large opening tion correction and artefact suppression in order (78 cm) is an important design improvement to support the clinical research protocols. In par- In the PET Section brain research continues on over the previous generation of systems. ticular for quantitative results in brain scanning, the PET-only HRRT (High Resolution Research the lack of direct attenuation measurements was Tomograph) in close collaboration with the Neu- The 128 slice PET/CT is installed in the KF Section. a challenge, and we have been addressing these robiology Research Unit (NRU), but the system This scanner mainly performs paediatric PET scans issues in collaborations with Siemens (Erlangen also works as a unique clinical instrument. and scans with 82Rb (heart perfusion), 68Ga-Dotatoc and Knoxville), University of Leuven and the in- The 6 PET/CT's in the department are all Siemens (neuroendocrine tumours) and 18F- NaF, replacing stitute of Computer Science at Copenhagen systems. 2 are Biograph TrueV, 1 with 40 and 1 some bone scintigraphy or SPECT/CT. University, resulting in a correction method which with 64 slice CT, acquired in 2007 and 2009. The is clinical feasible and with high precision. other 4 (from 2010, 2011, 2014 and 2016) are The fully integrated PET/MR scanner (Siemens mCT's, 3 with 64 slice CT and 1 with 128 slices, all mMR) was among the first in the world to be- Recently the PET/MR installation was comple- of them with time-of-flight and overall with very come operational in early 2012. Previous attempts mented with an MR hyperpolarizer (GE SPIN- similar specifications, which provides an important to combine the two modalities were either limited lab), allowing the production of 13C-labelled flexibility in patient scheduling. in use (brain “insert” only) or not fully integrated pyruvate, although not yet for human use. (two separate gantries). In the mMR a new The majority of the studies in the PET Section amplifier principle in the PET detectors made At the Cluster for Molecular Imaging at Panum, continue to be FDG whole-body scans for cancer them insensitive to the magnetic field and small the Faculty of Health Sciences, University of Co- diagnosis, staging, planning and follow-up, but enough to allow the PET scanner’s detector ring penhagen, we also operate 3 research scanners for in therecent years a significant number of FET, to be placed inside the 3-tesla MR-magnet be- PET and CT of small animals. The “older” systems FLT, 11C-PiB, and 68Ga-Dotatoc examinations tween the gradient coils and the RF transmitter. (from 2006) are a separate PET (Focus 120) and CT have been added. All these scans are routinely This made it possible to perform truly simulta- (microCAT II). More recently, an integrated PET/CT performed with the use of combined PET and CT, neous measurements of PET or MR. The combined system, the Inveon, was acquired and a Bruker 7T and most CT scans are performed as full diagnos- scanner offers better soft tissue differentiation MR scanner for small animals was installed.

48 department of clinical physiology, nuclear medicine & pet Equipment 2016

Equipment Product Purchase year Equipment Product Purchase year Mediso Nucline X-Ring 2003 Siemens mMR 2011 PET/MR scanner Mie-Scintron 2004 GE SPINlab MR Hyperpolarizer 2014 Mediso TH45 2007 Jaeger Masterscreen w/bodybox 2005 Gamma cameras Mediso N-TH45-D 2008 Lung function Jæger Masterscreen w/bodybox 2007 DDD SoloMobile 2012 Jaeger PFT pro w/bodybox 2007/13 DDD NephroCam System 2016 GE Lunar Prodigy 2004 Philips ADAC Skylight 2002 GE Lunar Prodigy 2005 SPECT cameras DXA scanner Mediso Nucline X-Ring-R/HR 2009 GE Lunar Prodigy 2011 GE Infinia Hawkeye 2004 GE Lunar iDXA 2014 Siemens SymbiaT2 2006 WBC w/Nal counting chamber 1977 Whole body counter Philips, Precedence 16-slice CT 2006 WBC w/plast counting chamber 1978 SPECT/CT cameras Philips, Precedence 16-slice CT 2008 Scanditronix 32 MeV 1991 Cyclotrons GE Discovery 670 2010 RDS Eclipse cyclotron, CTI 2005 Siemens Symbia 16-slice CT 2011 Provivo/ ADAC mobile gamma camera 1990 PET scanner HRRT Siemens/CTI 2007 Siemens Micro-PET Focus 120 2006 Siemens Biograph TrueV 40-slice CT 2007 Siemens preclinical CT Micro-CAT II 2006 Siemens Biograph TrueV 64-slice CT 2009 At Cluster for Phosphor Imager Perkin Elmer cyclone 2007 Molecular Imaging, Siemens mCT-S (64) 2010 Bruker preclinical MRI PharmaScan 7T 2013 PET/CT scanner Panum Siemens mCT-S (64) 2011 Siemens preclinical PET/CT Inveon 2013 Siemens mCT-S (128) 2013 PX Inc. preclinical RT X-RAD 320 2013 Siemens mCT-S (64) 2016 Mediso nanoScan SPECT/CT 2015

50 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 51 Academic and other activities

Andreas Kjær, Professor, Consultant, ERC ad- an Organisation for Research and Treatment of ryngeal cancer. Board member of DGCG (Danish and Services Committee in European Society for surgical Society (DNKS), responsible for the spe- Kim Francis Andersen, Consultant, is member of vanced grantee, is member of the Oncology Com- Cancer Lymphoma Group ” (EORTC), the Danish Gynecological Cancer Group) and DCCG (Danish Magnetic Resonance in Medicine and Biology cialist training course in the central nervous sys- the Board of Danish Sarcoma Group (DSG). He is mittee of the European Association of Nuclear Society of Radiology, the Danish and the Nordic Colorectal Cancer Group). (ESMEMB). tem for nuclear medicine physicians. involved in various clinical research protocols. He Medicine (EANM), national representative of the Society of Gynaecological Oncology, British insti- teaches at specialist courses for medical doctors European Society for Molecular Imaging (ESMI), tute of Radiology (BIR), Billeddiagnostisk udvalg Egill Rostrup, MSc, MD, DMSc,​ Consultant, Henrik B.W. Larsson, MD, DMSc , Consultant, Jacob Madsen, Chief Radiochemist Production and is supervisor for students at the Medicine board member of the Cancer Research Founda- Ukendt Primærtumor (DAHANCA), National PET/CT Member of the editorial board of the Journal of Head of Functional Imaging Unit. Professor in Manager, is member of the board of DSKFNM and Technology program (Biomedical Engineer- tion at University of Copenhagen, previous mem- Group, the Danish Society of Clinical Oncology, Cerebral Blood Flow and Metabolism, Steering Clinical and Comparative Physiology, Institute (Danish Society of Clinical Physiology and Nucle- ing), Technical University of Denmark (DTU). ber of the Scientific Committee of the Danish the Danish Society of Magnetic Imaging and committee of the Healthy Aging Clinical Neuro- of Clinical Medicine, The Faculty of Health and ar Medicine). He is an external reviewer at the Czech Science Cancer Society and President of the Scandinavian Diagnostic Imaging Group under Danish Lymphoma project at Glostrup, and the The Lundbeck Medical Science, University of Copenhagen, Foundation in the field of sarcomas. Society of Clinical Physiology and Nuclear Medi- Group, ERS European Society of Radiology. Foundation, Center for Clinical Intervention and Denmark, Representing Professor (ordførende Jann Mortensen, Clinical Associate Professor, cine (SSCPNM). Member of the National Cancer Neuropsychiatric Schizophrenia Research. professor) in Clinical Physiology and Nuclear Consultant, is member of “Den Regionale Viden- Linda Kragh, Chief Nuclear Medicine Technolo- Institute (NCI) white paper writing group on use Anne-Mette N. Wittekind, MSc. Pharm., Deputy Medicine, Institute of Clinical Medicine, The Fa- skabsetiske Komité F for Hovedstaden” (Regional gist, is member of Sundhedsfagligt Råd i Klinisk of hyperpolarized 13C MR, advisory board mem- Qualified Person, is member of Dansk Standard. Elisabeth Albrecht-Beste, Clinical Associate culty of Health and Medical Science, University Ethics Committee). He is responsible for the spe- Fysiologi og Nuklearmedicin i Region H, SFR, ber of the Avatar Cancer Program, CPMC (Sutter Professor, Consultant, is board member of Danish of Copenhagen, Denmark, Professor in Medical cialist course in “Clinical Respiratory Physiology” (the Speciality Advisory Committee in Clinicial Health), San Francisco. Editor-in-Chief of Diag- Annika Loft Jakobsen, Consultant, is involved in Society of Radiology, chair of post-graduate Magnetic Resonance Imaging, Norwegian Uni- for Nuclear Medicine physicians and Respiratory Physiology and Nuclear Medicine in the Capital nostics (Basel). Editorial board member of Jour- a various number of clinical research protocols, radiology courses in Denmark, chair of post- versity of Science and Technology, Norway, Re- Physicians, he is the responsible physician for Region), member of the DRG Committee of DSKFNM, nal of Nuclear Medicine (JNM) and European teaching at national and international courses graduate education committee of Danish Society sponsible for specialist course in tracer kinetic Nuclear Medicine in the Faroe Islands, member member of Uddannelsesforum for bioanalytiker- Journal of Nuclear Medicine & Molecular Imag- pre- and postgraduate for medical doctors, tech- of Radiology, chair of the Regional Advisory theory, math and statistic for nuclear medicine of the steering committee of “Dansk Lungecancer uddannelsen i Region H, (the Speciality Council ing (EJNMMI). Leader of projects for develop- nologists, radiographers and nurses and is invited Board in postgraduate education in radiology and physicians. Responsible for specialist course in Gruppe” (Danish Lung Cancer Group), the sub- for the Education of Technologists in the Capital ment of theranostics for aggressive cancer and speaker at national and international meetings member of the Danish Society of Oncoradiology. functional imaging (MRI, PET-MRI, UL) for nucle- committees for “Dansk Diagnostisk Lungecancer Region) and member of Uddannelsesudvalget på for project of hyperPET, funded by the Innovation and congresses. She is supervisor for several PhD ar medicine physicians, Management board of EU Gruppe” (Danish Diagnostic Lung Cancer Group) Radiografuddannelsen at Metropol (the Speciality Fund Denmark. Coordinator of an H2020 project students and responsible for the specialist course Helle Hjorth Johannesen, Consultant, is mem- COST Action (BM1103): “Arterial Spin Labelling and “Lungecancer Screeningsgruppen” (Screen- Council for the Education of Radiographers at on click-chemistry for PET. National Director of in oncology for nuclear medicine physicians. She ber of Danish Society of Radiology, President of in Dementia”, Steering committee of the 7 Tesla ing of Lung Cancer Group), member of the steer- Metropol). EATRIS (the European Advanced Translational is a member of the “European Organisation for Danish Society of Oncoradiology, member of Danish project, Copenhagen, Denmark. ing committee and the quality subcommittee for Research Infrastructure in Medicine), Head of the Research and Treatment of Cancer” (EORTC). Society of Medical Magnetic Resonans Imaging creating Danish reference values for lung func- Lise Borgwardt, Consultant, is Scientific Com- Cluster for Molecular Imaging and Director of the Member of the Oncology Committee of EANM, and Danish Society for Good Clinical Practice. Ian Law, Professor, Consultant, is Chair of the tion, and member of the steering committee of mittee member of the EANM, Vice Chair of the PhD Program for Medical & Molecular Imaging at and member of BIR, Danish Society of Oncologial Neuroimaging Comittee, European Association of the Danish ESDL spirometry course. Paediatric Committee under EANM, member of the the Faculty of Health and Medical Sciences, Uni- Radiology and Danish Society of Clinical Physiol- Helle Juhl Simonsen, Research MRT, Biomedical Nuclear Medicine (EANM), Member of the “PET Paediatric Imaging Harmonization Group, member versity of Copenhagen. Co-chair of the Lundbeck ogy and Nuclear Medicine. Member of Regional Laboratory Scientist, is board member and treasu- Response Assessment in Neurooncology (RANO) Johan Löfgren, Consultant, teaches at specialist of the Tumourboard for Paediatric Solid Tumours Foundation Clinical Research Fellowship Program Working Groups for implementation of clinical rer in the International Society for Magnetic working group” under the European Association courses for oncologists and is a member of the at Rigshospitalet, Chair of the Paediatric Focus (US-DK). Member of the Academy of Technical guidelines for: colorectal liver metastases, lym- Resonance in Medicine (ISMRM)/Nordic Chap- of Nuclear Medicine (EANM), European Associ- Diagnostic Imaging Group under Danish Lym- Group at the Department of Clinical Physiology, Sciences (ATV). phoma, malignant melanoma, cancer of unknown ter. Member of the Local Chapters Committee, ation of Neurooncology (EANO), and Society of phoma Group. He is involved in clinical research Nuclear Medicine and PET and member of the primary, and suspicion of severe disease. Member Awards and Nominations Committee and Abstract Neurooncology (SNO). Member of the Danish protocols with special focus on PET/MRI and is Process Group for the development of the Chil- Anne Kiil Berthelsen, Consultant, is member of of National Working Groups for lymphoma (Chair Committee in International Society for Magnetic Neurooncology group (DNOG). Member of the an invited speaker at national and international dren’s Hospital at Rigshospitalet. She is involved the International Lymphoma Radiation Oncology of the Diagnostic Imaging Group under Danish Resonance in Medicine (ISMRM)/Section for MR working group for ”Clinical Guidelines for the meetings and congresses. in clinical research protocols, supervisor for PhD Group, Steering Committee (ILROG), “Europe- Lymphoma Group (DLG)) and pharyngeal/la- Technologist (SMRT), Member of the Members Treatment of Brain Metastases”, Danish Neuro- students, teaching at national and international

52 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 53 Academic and other activities

courses pre- and postgraduate for medical doc- Louise Alslev, Staff Specialist, is responsible for Marie Øbro Fosbøl, PhD Student, President of the Niels A. Lassen Foundation. He is co-editor at EFOMP’s School for Medical Physics Experts vascular circulation for nuclear medicine physi- tors, and is invited speaker at national and inter- the planning of educational visits for physici- Society of Young Nuclear Medicine Physicians for the Danish Medical Journal in the medical and Copenhagen University. cians in Denmark. Member of the Danish Society national meetings and congresses. ans at the PET Section at Rigshospitalet. She (YNK, member of the board of Danish Society of imaging section. He is responsible for the post- of Clinical Physiology and Nuclear medicine, teaches at a PhD course at the Faculty of Health Clinical Physiology and Nuclear Medicine (DSK- graduate education in the Glostrup Section of the Søren Holm, Senior Physicist, is a member of the Danish Society of Cardiology and Danish Society Lisbeth Marner, MD, PhD, DMSc, Staff specialist, and Medical Sciences, University of Copenhagen FNM) and member of the course committee in department. EANM Physics Committee and the newly founded of Diagnostic Ultrasound. is a member of European Society for Paedicatric and at the Bachelor´s Degree Program in Radio- clinical physiology and nuclear medicine. EANM Radiation Protection committee, and has Oncology (SIOPE) Imaging group; responsible graphy at the Metropolitan University College. Peter Oturai, Consultant, is responsible for the represented EANM in meetings with IAEA and for specialist course in tracer kinetic theory, math Employee representative for the junior doctors at Nic Gillings, MPhil, PhD, Chief Radiochemist, postgraduate education of physicians in the de- HERCA (Heads of European Radiation Compe- and statistic for nuclear medicine physicians; the Centre of Diagnostic Investigation, Rigshospi- Qualified Person (QP) is a member of the EANM partment. He is Danish delegate, representing tent Authorities). He is a delegate for DSMF to responsible for a large imaging study in children talet. Member of Yngre Læger-rådet (Counsel of Radiopharmacy Committee, member of the Soci- Danish Society for Clinical Physiology and Nucle- the European and International organisations for with CNS cancer, teaches at several PhD courses Junior Doctors) at Rigshospitalet. ety of Radiopharmaceutical Sciences and member ar Medicine (DSKFNM), in the European Union Medical Physics (EFOMP and IOMP), board mem- as well as pregraduate courses for Medicine and of the Royal Society of Chemistry. He also acts as of Medical Specialists (UEMS) and deputy dele- ber of the Nordic Society for Radiation Protection Technology Bioengineers, is a member of the Malene Fischer, Associate Professor of Research, coordinator for the joint supplier audit program gate in the European Association of Nuclear (NSFS), member of one IAEA advisory group con- Danish CNS Interest Group and is accountant for Consultant, is supervisor for several PhD students for all manufacturers of PET radiopharmaceuti- Medicine (EANM). He has been representing cerned with QA/QC and image artefacts affecting the Young Nuclear Medicine Club (YNK). and involved in both pre- and postgraduate cals in Denmark and Southern Sweden. DSKFNM in the Danish Health and Medicines SPECT/CT and another IAEA advisory group teaching. Course Director of “Introduction to Authority’s committee for speciality planning regarding staffing in medical physics, member of Liselotte Højgaard, Professor, Head of Depart- Clinical Medical Imaging” at the Medicine and Otto Mølby Henriksen, Consultant, PhD, is of Clinical Physiology and Nuclear Medicine Sundhedsfagligt Råd i Klinisk Fysiologi og Nuklear- ment. Chairman of the Board of the Danish Technology Bioengineer program, member of member of the DRG Committee in Danish Socie- (CPNM). He is member of the Danish Thyroid medicin in the Capital Region, the Specialty Advi- National Research Foundation. She is Member the European Association of Nuclear Medicine ty for Clinical Physiology and Nuclear Medicine Cancer Guideline Group (DATHYRCA), member sory Committee (SFR) in Clinical Physiology and of Conseil d’Administration, INSERM, Institut (EANM) and the Danish Society of Clinical Physi- (DSKFNM). Supervisor of one research year stu- of the Doctors CPNM Training Committee and Nuclear Medicine and external lecturer at Univer- National de la Santé et de la Recherche Médicale, ology and Nuclear Medicine (DSKFNM). Affiliat- dent and co-supervisor of one PhD student. member of the CME and Educational Committee sity of Copenhagen. Frankrig. Chair of EU Science Advisory Board in ed to the Centre of Excellence for Personalized – both affiliated to DSKFNM. He is responsible Health Research. Member of the Board, Konsisto- Medicine of Infectious Complications in Immune Peter Hovind, Consultant, participates in several for the specialist course in Endocrine Pathophysio- Thomas Levin Klausen, Chief Physicist, MSc, riet, the Karolinska Institute. She represents the Deficiency (PERSIMUNE) and the steering com- clinical research protocols. He is the President logy for CPNM physicians in Denmark. Specialist Medical Physicist, Chair of Danish University of Copenhagen, Rigshospitalet in the mittee of MATCH (Managing of Post-Transplant of the Danish Society of Clinical Physiology and Society for Medical Physics Educational Council, Medicine and Technology Bioengineer program, Infections in Collaborating Hospitals). Elected Nuclear Medicine. At present, he is also the Head Rasmus Sejersten Ripa, Staff Specialist, is su- member of the Danish Society for Medical Physics the Technical University of Denmark (DTU), member of the board of representatives, the of the specialist courses in Clinical Physiology pervisor for several PhD students. Member of the (DSMF) and the Danish Society of Clinical where she is also adj. professor. Elected Member Association of Consultants in Denmark. and Nuclear Medicine under the Danish Health Danish Health Authority’s Committee for Heart Physiology and Nuclear Medicine (DSKFNM). of the Royal Danish Academy of Sciences and and Medicines Authority, where he is responsible Disease. He is co-editor of BMC Cardiovascular Responsible Physicist for Nuclear Medicine in the Letters, member of ATV “The Danish Academy of Maria Helene Pejtersen, Nuclear Medicine Tech- for the theoretical part of the specialist training Disorders and member of American Society of Faroe Islands. Technical Sciences”, member of the Olav Thon nologist, is member of the Symposiagroup for in Clinical Physiology and Nuclear Medicine in Nuclear Cardiology. ​ Foundation, Science Advisory Board, member Technologists at Rigshospitalet. Denmark. He is the Head of the Doctors Clinical Ulrik B. Andersen, Consultant, Co-supervisor of the Board of the Crown Prince Frederik and Physiology and Nuclear Medicine Training Com- Robin de Nijs, MSc, PDEng, PhD, Specialist for PhD students in the department. Member of Crown Princess Mary’s Foundation and member Marianne Federspiel, Nuclear Medicine Technolo- mittee of the Danish Society for Clinical Physi- Medical Physicist, is member of EANM’s Network European Society of Hypertension and acknowl- of the Board of Arvid Nilssons Foundation and gist, Senior Consultant to the EANM Technologists ology and Nuclear Medicine and a member of the of Excellence for Brain Imaging, member of the edged hypertension specialist by this society. Tagea Brandt’s prize. Committee. board of the Danish Endocrine Society (DES) and Danish Society for Medical Physics and lecturer Responsible for the specialist course in cardio-

54 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 55 Studies 2016

CNS and peripheral nervous system Heart and cardiovascular system Glomerular filtration,51 Cr-EDTA, one sample 3,593 Iodine uptake test, 131I-Iodide 26 15 99m 99m 99m Regional cerebral blood flow, DIAMOX, O-H2O 12 Isotope cardiography, LVEF, Tc-HSA 1,460 Renal scintigraphy, Tc-DMSA 25 Parathyroid scintigraphy, Tc-Stamisis 11 18 99m 99m 99m Regional cerebral metabolism, F-FDG 1,029 Myocardial perf. scintigr. gated, Tc-MIBI, pharmacol. stress, adeno. 195 Renography, Tc-MAG , diuresis 41 Parathyroid scintigraphy, Tc-Stamisis, SPECT 36 11 99m 99m 123 Regional cerebral receptor, C-PIB 168 Myocardial perf. scintigr. gated, Tc-MIBI, psysiological. stress 2 Renography, Tc-MAG 3, graft 2 Tumourscintigraphy, I-Iodide 1 Regional cerebral receptor, 18F-FET 465 Myocardial perf. scintigr. gated, 99mTc-MIBI, 165 Renography, 99mTc-MAG 3, ACE-inhibitor 22 Tumourscintigraphy, 123I-Iodide, rh-TSH 13 Regional cerebral blood flow,99m Tc- HMPAO, pharm.prov. 13 Myocardial 123I- MIBG, sympaticus activity 70 Renography, 99mTc-MAG 3 2,256 Adrenal marrow scintigraphy, 123I-MIBG 43 99m 99m 177 Regional cerebral blood flow, Tc- HMPAO 51 Myocardial calcium score 611 Renography, Tc-MAG 3, dual head 8 Scintigraphy after Lu- Dotatate therapy 132 Regional Dopamine Transporter (DAT) receptor imaging, 123I-FP-CIT 271 Tilt table test 273 Renography, 99mTc-DTPA 34 Synacthen test 107 Regional cerebral receptor, 11C different tracers human (NRU) 78 Analysis of heart rate variability 295 Renography, 99mTc-DTPA, ACE-inhibitor 221 Total 2,590 Regional cerebral receptor, 11C differenct tracers animal (NRU) 49 PET myocardial metabolism, 18F-FDG 96 Doppler ultrasound of renal blood flow 430 Regional cerebral receptor, 18F-Florbetapir 19 PET myocardial perfusion, 82Rb 651 Ultrasound kidneys 411 Blood and lymph system Regional cerebral receptor, 18F-FLT 11 PET myocardial perfusion, 82Rb, pharmacological stress, adeno 628 CT kidneys 87 Erythrocyt volume, 99mTc-erythrocytter 57 Regional cerebral receptor, 68Ga-Dotatoc 28 CT cardiac angiography 70 CT bladder 87 Plasma volume, 125I-HSA 57 CT-scanning of cerebrum 212 Total 4,516 Total 1,270 Lymph scintigraphy, extremities, 99mTc-HSA, leakage 1 MR-scanning of cerebrum 2,764 Sentinel node scintigr. tumour drainage, 99mTc-Nanocolloid 14 Total 5,170 Peripheral vessels Bone and joint Sentinel node scintigr. tumour drainage, c. mammae, 99mTc-Nanocolloid 34 Systolic blood pressure, fingers 2 Bone scintigraphy, 99mTc-HDP, regional, static 70 Sentinel node scintigr. tumour drainage, mel. malign., 99mTc-Nanocolloid 158 Respiratory organs Systolic blood pressure, ancle and toes 407 Bone scintigraphy, 99mTc-HDP, 2 phased 8 Sentinel node scintigr. tumour drainage, c. penis, 99mTc-Nanocolloid 22 Lung function test, whole body plethysmography 2,074 Systolic blood pressure, ancle-brachial index after treadmill 87 Bone scintigraphy, 99mTc-HDP, whole body, static 755 Sentinel node scintigr. tumour drainage, c. vulvae, 99mTc-Nanocolloid 33 Lung function test, whole body plethysmography w/reversibility 55 24 hours blood pressure measurement 262 Bone scintigraphy, 99mTc-HDP, SPECT 724 Sentinel node scintigr. tumour drainage, head/neck SPECT, 99mTc-Nanocolloid 93 Lung function test, spirometry, 2,230 Doppler ultrasound of carotid arteries 4,113 Bone scintigraphy, 18F-fluorid, whole body, static 3 Sentinel node, peroperative with gamma probe, 99mTc-Nanocolloid 1 Lung function test, spirometry w/reversibility 214 Doppler ultrasound of abdominal vessels 470 Osteodens. dual X-ray absorptiometri (DXA), columna lumb. 4,725 Peritumoural injection of 99mTc-Nanocolloid for sentinel node 631 Lung function test, diffusion capacity (CO) 4,079 Isolated limb perfusion leakage monitoring, 99mTc-erythrocyt 6 Osteodens. dual X-ray absorptiometri (DXA), lat.spine 445 Spleen scintigraphy, 99mTc-erythrocyte, heated 3 Lung function test, spirometry with phys.prov. 5 Total 5,347 Osteodens. dual X-ray absorptiometri (DXA), radius 144 Total 1,104 Max. insp. abd exspir. muscle pressure 54 Osteodensitometri, dual X-ray absorptiometri collum fem. 9,252 Lung perfusion scintigraphy, 99mTc-MAA 1 Gastrin intestinal tract, liver, biliary tract and pancreas DXA, body composition 633 Other diagnostic procedures Lung perfusion scintigraphy, regional, 99mTc-MAA 9 Salivary gland scintigraphy 99mTc-Pertechnetat 22 MR scanning columna cervicalis 2 Aprotinin scintigraphy, 99mTc-Aprotinin 2 Lung perfusion scintigraphy, SPECT, 99mTc-MAA 386 Biliary tract scintigraphy, 99mTc-Mebrofenin 90 MR scanning wrist 34 Tumourscintigraphy 111In-Octroetid 1 Lung ventilation scintigraphy, 81mKr-gas 19 Bleeding scintigraphy (abdomen) 99mTc-erytrocytter 4 Total 16,795 PET tumour scanning, 18F-FDG 5,226 Lung ventilation scintigraphy, regional, 81mKr-gas 113 Bleeding scintigraphy (abdomen) 99mTc-HSA 1 PET scanning, 18F-FDG 219 Lung ventilation scintigraphy, SPECT, 81mKr-gas 341 Doppler ultrasound of splanchnic blood flow 430 Endocrine organs PET infection scanning, 18F-FDG 163 Lung ventilation scintigraphy, SPECT 99mTc-Technegas 57 Glucose tolerance test 10 Thyroid scintigraphy, 99mTc-Pertechnetat 1,048 PET tumour scanning, 68Ga-DOTATOC 681 Mucociliary clearance, 99mTc-Venticolloid 8 Total 557 Thyroid scintigraphy, 123I-Iodide 28 White blood cell scintigraphy, 99mTc-white blood cell 13 CT thorax PET/CT breathhold 23 Thyroid, ultrasound 1,091 White blood cell scintigraphy, 99mTc-white blood cell, SPECT 21 Total 9,668 Kidneys and urinary tract Thyroid scintigraphy, 99mTc-Pertechnetat, SPECT 1 White blood cell scintigraphy, 111In-white blood cell 2 Glomerular filtration,51 Cr-EDTA, several samples 89 Thyroid, fine needle aspiration biopsy 53 White blood cell scintigraphy, 99mTc-leucoscan, SPECT 1

56 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 57 Studies 2016 Finance

Assessment of blood samples 18 Animal studies Radiotherapy, 177Lu-X 7 Turnover 177 Whole body, contamination measurement 104 Radiotherapy, Lu-ASIS 206 Image fusion (PET, SPECT, MRI, CT or planar) 10,689 Mice Radiotherapy, alpha emitters 36 300 CT head/neck SPECT/CT 241 11C-Tetrazine 26 CT-scans 178 CT wb SPET/CT 534 18F-ASIS 39 CT-scans for image fusion 1,167

CT thorax SPECT/CT 485 18F-Apopep 6 K 250 Rats CT pelvis SPECT/CT 55 18F-FDG 215 18F-FDG 102 CT abdomen SPECT/CT 264 18F-FET 145 200 64Cu-liposomes 144 CT lower extremities SPECT/CT 7 18F-FLT 254 82Rubidium 77 CT wb PET/CT (KF) 1,361 52Mn-liposome 90 Optical imaging, bioluminescence 85 150 CT wb PET/CT (PET) 5,368 64Cu 5 MR-scans 60 MR wb PET/MR 107 64Cu-ASIS 36 MR-scans DWI 2 100 CT lover extremities PET/CT 15 64Cu-DOTA-AE105 20

MR-spectroscopy 8 Krone points in mio DK Ultrasound, various 15 64Cu-liposome 543 Radiotherapy, externally 6 50 Second opinions external 1,112 64Cu-liposome targeted 96 CT-scans for image fusion 258 Extra tumour delineation 148 64Cu-X 6 Other investigations 189 68Ga-NOTA-AE105 20 Dogs 0 Supplementary/repeated imaging 2,713 68Ga-RGD 48 18F-ASIS/13C-pyruvate 1 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Total 29,754 89Zr-Heceptin 167 18F-FDG/13C-pyruvate 13 99mTc-DMSA 16 64Cu-liposome 3 Year Radiotherapy 111In-Tetrazine 62 68Ga-RGD/13C-pyruvate 2 Treatment with 131I, benign thyroid 81 124I-liposome 40 MR-scans for image fusion 16 The increase in activities measured in krone point* rose from 72,6 mio DKK in Isotope treatment with 177Lu-Dotatate 121 134Ce-AE105 5 CT-scans for image fusion 3 2006 to 258,7 mio DKK in 2016. Isotope treatment with 223Ra-Dichlorid 213 134CE-ATN291 5 Rabbits Total 415 140ND-AE105 5 18F-Apopep 1 * Krone point: Price for each patient investigation multiplied with number of 140ND-ATN291 5 68Ga-RGD 44 investigations, summarized for all patient studies performed during the year. In vitro analyses 177Lu-ASIS-ionphore 33 Affinity studies 4.067 177Lu-ASIS-SPECT 14 Pigs Flow cytometry analyses 9.987 177Lu-DOTATATE 2 18F-FDG 3 Gene expression analyses 10,838 177Lu-X 2 Immunohistochemistry 1,005 Optical imaging, bioluminescence 1,095 Total 7,164 Plasma and protein analyses 1,344 Fluorescence imaging, ICG-Glu-Glu-AE105 24 Balance 2016 Total 27,241 MR-scans 1,145 MR-scans DWI 245 Expenditure (DKK mio ) 94 Radiotherapy, externally 321 Total number of studies 111,591 Receipts 17 Radiotherapy, 177Lu-DOTATATE 7

58 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 59 Publications

Theses memory recall, simple reaction time, and mental Agn M, Law I, Munck af Rosenschöld P, Van L, Koen. L, Røder MA, Bjartell A. Automated Bone Scan in chronic cluster headache patients through 24 Byrne C, Enevoldsen LH, Kjær A, Hasbak P. Impaired th Suetta C. Doctoral thesis. Plasticity and function of distress. Defended on the 14 of January 2016. A generative model for segmentation of tumor Index as a quantitative imaging biomarker in months. J Headache Pain. 2016 Dec;17(1):67. cardiac PET image quality due to delayed 82 human skeletal muscle in relation to disuse and University of Copenhagen. and organs-at-risk for radiation therapy planning metastatic castration-resistant prostate cancer Barloese MCJ. A Review of Cardiovascular Rubidium dose delivery to the heart. rehabilitation: Influence of ageing and surgery, Tønnesen R. PhD thesis. Vitamin D status in young of glioblastoma patients. Society of Photo-Optical patients being treated with enzalutamide. Autonomic Control in Cluster Headache. J Nucl Cardiol. 2016 Oct;23(5):1173-5. Defended on the 20th of May 2016, University of adults in Denmark – Implications for bone Instrumentation Engineers (SPIE) Medical EJNMMI Res 2016 Dec;6(1):23. doi: 10.1186/ Headache. 2016 Feb;56(2):225–39. Brittain JM, Kvist N, Johansen LS, Borgwardt L. Copenhagen. mineral density, renin angiotensin-system & Imaging: Image Processing. 2016;9784: D-9. s13550-016-0173-z. Benoit D, Ladefoged C, Rezaei A, Keller SH, Hepatobiliary scintigraphy for early diagnosis of th Andersen JB. PhD thesis. Neonatal Imaging of sympathetic nervous system. Defended on the 29 Albert NL, Weller M, Suchorska B, Galldiks N, Andersen KF, Jensen KE, Loft A. PET/MR Imaging Andersen F, Hojgaard L, Hansen AE, Holm S, biliary atresia. Dan Med J. 2016 Aug;63(8):1-5. Cerebral Blood Flow with Positron Emission of September 2016. University of Copenhagen. Soffietti R, Kim MM, la Fougere C, Pope W, Law in Musculoskeletal Disorders. PET Clin 2016 Nuyts J. Optimized MLAA for quantitative non- Brittain JM, Borgwardt L. Potential pitfalls on the 99m Tomography and Arterial Spin Labeling Magnetic Zornhagen KW. PhD thesis. Hypoxia imaging in I, Arbizu J, Chamberlain MC, Vogelbaum M, Oct;11(4):453-63. TOF PET/MR of the brain. Phys. Med. Biol. 2016 Tc-Mebrofenin hepatobiliary scintigraphy in a Resonance. Defended on the 18th of May 2016. dogs with PET and correlation with key molecular Ellingson BM, Tonn JC. Response Assessment in Arngrim N, Schytz HW, Britze J, Amin FM, Dec;61(24):8854–8874. patient with biliary atresia splenic malformation nd University of Copenhagen. hypoxia markers. Defended on the 22 of Neuro-Oncology working group and European Vestergaard MB, Hougaard A, Wolfram F, de Berg RMG, Plovsing RR, Bailey DM, Holstein- syndrome. Diagnostics 2016 Jan;6(5):1-3. la Cour JL. PhD thesis. Radiation Induced January 2016, University of Copenhagen. Association for Neuro-Oncology recommendations Koning PJ, Olsen KS, Secher NH, Larsson HB, Rathlou N-H, Møller K. Dynamic cerebral da Cunha-Bang S, Mc Mahon B, Fisher PM, Jensen Atherosclerosis – A Possible Side Effect of for the clinical use of PET imaging in gliomas. Olesen J, Ashina M. Migraine induced by hypoxia: autoregulation to induced blood pressure changes PS, Svarer C, Knudsen GM. High trait aggression Radioiodine Therapy. Defended on the 5th of Neuro Oncol. 2016 Sep; 18(9):1199-208. an MRI spectroscopy and angiography study. in human experimental and clinical sepsis. in men is associated with low 5-HT levels, as February 2016. University of Copenhagen. Patents Alzahrani M, El-Galaly TC, Hutchings M, Hansen Brain. 2016 Mar;139(Pt 3):723-37. Clinical physiology and functional imaging. indexed by 5-HT4 receptor binding. Soc Cogn da Cunha-Bang S. PhD thesis. Multimodal Kjær A (with co-inventors). Entrapment of JW, Loft A, Johnsen HE, Iyer V, Wilson D, Sehn Asghar MS, Becerra L, Larsson HB, Borsook D, 2016;36(6):490-96. Affect Neurosci. 2016 Apr;11(4):548-55 Neuroimaging of Aggression in Violent Offenders. radionuclides in nanoparticle compositions. LH, Savage KJ, Connors JM, Gascoyne RD, Ashina M. Calcitonin gene-related peptide Berg RMG, Plovsing RR, Greve AM, Christiansen Dreier R, Asferg C, Berg JO, Andersen UB, Flyvbjerg A, Defended on the 8th of July 2016. University of US-9226984B2. January 5, 2016 Johansen P, Clasen-Linde E, Brown P, Villa D. The modulates heat nociception in the human brain- CB, Toksvang LN, Holstein-Rathlou N-H et al. Frystyk J, Linneberg A, Jeppesen JL, Edvinsson L, Copenhagen. Kjær A (with co-inventors). Upar targeting peptide value of routine bone marrow biopsy in patients An fMRI study in healthy volunteers. Plos One. Spontaneous blood pressure oscillations in Skovsted GF. Similar Adiponectin Levels in Obese Johnbeck CB. PhD thesis. Positron emission for use in peroperative optical imaging of invasive with diffuse large B-cell lymphoma staged with 2016 Mar;11(3):e0150334. mechanically ventilated patients with sepsis. Normotensive and Obese Hypertensive Men and tomography for neuroendocrine tumors. cancer. WO-2016041558A1. March 24, 2016. PET/CT: a Danish-Canadian study. Annals of Asmar A, Simonsen L, Asmar M, Madsbad S, Holst Blood Pressure Monitoring. 2016;21(2):75-9. No Vasorelaxant Effect of Adiponectin on Human Defended on the 20th of May 2016, University of Olesen OV (with co-invenstors). Apparatus and Oncology. 2016 jun;27(6):1095-9. JJ, Frandsen E, Moro C, Sorensen CM, Jonassen Bloomquist K, Hayes S, Adamsen L, Møller T, Arteries. Basic Clin Pharmacol Toxicol. 2016 Copenhagen. method for motion tracking in brain imaging. Amin FM, Hougaard A, Magon S, Asghar MS, T, Bülow J. Glucagon-like peptide-1 does not have Christensen KB, Ejlertsen B, Oturai P. Feb;118(2):128-35. Mc Mahon B. PhD thesis. Seasonal changes DK-2854637T3. June 13, 2016. Ahmad NN, Rostrup E, Sprenger T, Ashina M. acute effects on central or renal hemodynamics A randomized cross-over trial to detect differences Cejvanovic V, Asferg C, Kjær LK, Andersen UB, in cerebral serotonin transporter binding in Kjær A (with co-inventors). Positron emitting Change in brain network connectivity during in patients with type 2 diabetes without in arm volume after low- and heavy-load Linneberg A, Frystyk J, Henriksen T, Flyvbjerg individuals with or resilient to Seasonal Affective radionuclide labeled peptides for human uPAR PET PACAP38-induced migraine attacks: A resting- nephropathy. Am J Physiol Endocrinol Metab. resistance exercise among patients receiving A, Christiansen M, Weimann A, Jeppesen J, Disorder. Defended on the 1th of April 2016. imaging. US-20160263260A1. September 15, 2016 state functional MRI study. Neurology. 2016 2016 May;310(9):E744-53. adjuvant chemotherapy for breast cancer at risk Poulsen HE. Markers of oxidative stress in University of Copenhagen. Jan;86(2):180-7. Balslev H, Drotner K, Andersen NO, Højgaard for arm lymphedema: study protocol. obese men with and without hypertension. Nielsen CH. PhD thesis. Stratification of patients for Aneheim E, Gustafsson A, Albertsson P, Back L, Juselius K, Roepstorff A. Videnskabens BMC Cancer 2016 Jul;16:517. doi: 10.1186/ Scand J Clin Lab Invest. 2016 Dec;76(8):620- targeted EGFR therapy and monitoring of therapy Publications T, Jensen H, Palm S, Svedhem S, Lindegren betydning for samfundet. Det Kongelige Danske s12885-016-2548-y. 625. response by measurement of serum biomarkers Aagaard P, Jacobsen M, Jensen KY, Nielsen JL, S. Synthesis and Evaluation of Astatinated Videnskabernes Selskab. 2016;1-16. ISBN 978-87- Briegel A, Ortega DR, Mann P, Kjaer A, Ringgaard Christensen AN, Rydhög JS, Søndergaard RV, and PET imaging. Defended on the 1st of April Bülow J, Rørdam L, Suetta C, Frandsen U. N[2-(Maleimido)ethyl]-3- (trimethylstannyl) 7304-3984. S, Jensen GJ. Chemotaxis cluster 1 proteins Andresen TL, Holm S, Munck Af Rosenschöld 2016, University of Copenhagen. Effects of Chronic Blood-Flow Restriction Exercise benzamide Immunoconjugates. Bioconjugate Barloese MC, Jürgens TP, May A, Lainez JM, Schoenen J, form cytoplasmic arrays in Vibrio cholera and P, Conradsen K, Jølck RI. Injectable silver Stenbæk DS. PhD thesis. Sex steroid hormone on Skeletal Muscle Size and Myogenic Satellite Chem, 2016; 27(3):688–697. Gaul C, Goodman AM, Caparso A, Jensen RH. are stabilized by a double signaling domain nanosensors: in vivo dosimetry for external beam manipulations and serotonergic Cell Expression. Med Sci Sports Exerc. 2016 Anand A, Morris MJ, Larson SM, Minarik D, Cluster headache attack remission with receptor DosM. Proc Natl Acad Sci U S A. 2016 radiotherapy using positron emission tomography. neurotransmission in relation to verbal affective May;48(5 Suppl 1):1032-3. Josefsson A, Helgstrand JT, Oturai PS, Edenbrandt sphenopalatine ganglion stimulation: experiences Sep;113(37):10412-10417. Nanoscale. 2016 Jun 7;8(21):11002-11.

60 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 61 Publications

Christensen A, Juhl K, Charabi B, Mortensen J, Kiss Dejanović D, Alslev L, Abrahamsson E, Costa J, Loft with [11C]Cimbi-36: Test-retest reproducibility and Haissman JM, Knudsen A, Hoel H, Kjaer A, and blood volume using 18F-fluoroethyltyrosine Jakobsen GR, Fisher PM, Dyssegaard A, McMahon B, K, Kjær A, von Buchwald C: Feasibility of Real- A. A case of asymptomatic venous air embolism head-to-head comparison with the antagonist [18F] Kristoffersen US, Berge RK, Katzenstein TL, (FET) PET/MRI: feasibility, agreement and Holst KK, Lehel S, Svarer C, Jensen PS, Knudsen Time Near-Infrared Fluorescence Tracer Imaging demonstrated on 18F FDG PET/CT. Clin Nucl Med. altanserin. NeuroImage 2016 Apr;130:167-174. Svardal A, Ueland T, Aukrust P, Lebech AM, initial experience. Eur J Nucl Med Mol Imaging. GM, Frokjaer VG Brain serotonin 4 receptor binding in Sentinel Node Biopsy for Oral Cavity Cancer 2016 May;41(5):385-6. Feng L, Svarer C, Madsen K, Ziebell M, Dyssegaard A, Nielsen SD, Trøseid M. Microbiota-Dependent 2016 Jan;43(1):103-12. is associated with the cortisol awakening response. Patients. Ann Surg Oncol. 2016 Feb;23(2):565-72. Ebdrup BH, Raghava JM, Nielsen MØ, Rostrup Ettrup A, Hansen HD, Lehel S, Yndgaard S, Paulsen Marker TMAO Is Elevated in Silent Ischemia but Henriksen OM, Marner L, Law I. Clinical PET/MR Psychoneuroendocrinology. 2016 maj;67:124-32. Christensen CB, Borgwardt L, Loft A, Berthelsen AK. E, Glenthøj B. Frontal fasciculi and psychotic OB, Knudsen GM, Pinborg LH. Design of Infusion Is Not Associated With First-Time Myocardial Imaging in Dementia and Neuro-Oncology. PET Jakobsen JK, Alslev L, Ipsen P, Costa JC, Krarup PET/CT radiotherapy planning in children. EANM symptoms in antipsychotic-naive patients with Schemes for Neuroreceptor Imaging: Application Infarction in HIV Infection. J Acquir Immune Clin 2016 Oct;11(4):441-52. KP, Sommer P, Nerstrøm H, Toft BG, Høyer S, Vol. Part 3. 2016:67-71 schizophrenia before and after 6 weeks of to 11CFlumazenil-PET Steady-State Study. BioMed Defic Syndr. 2016 Feb;71(2):130-6. Henriksen OM, Larsen VA, Muhic A, Hansen AE, Bouchelouche K, Jensen JB. DaPeCa-3: Promising Christensen TE, Bang LE, Holmvang L, Hasbak P, Kjaer selective dopamine D2/3 receptor blockade. J Research International. 2016;2016:9132840. Haissman JM, Haugaard AK, Knudsen A, Larsson HBW, Poulsen HS, Law I. Simultaneous results af sentinel node biopsy combined with A, Bech P, Østergaard SD. Neuroticism, depression Psychiatry Neurosci. 2016 Mar;41(2):133-41. Fischer BM, Siegel BA, Weber WA, von Bremen K, Kristoffersen US, Seljeflot I, Pedersen KK, Lebech evaluation of brain tumour metabolism, structure 18F-fluorodeoxyglucose positron emission and anxiety in takotsubo cardiomyopathy. BMC Edem PE, Fonslet J, Kjaer A, Herth M, Severin G. In Beyer T, Kalemis A. PET/CT is a cost-effective tool AM, Hasbak P, Kjaer A, Ostrowski SR, Gerstoft and blood volume using [18F]-fluoroethyltyrosine tomography/computed tomography in clinically Cardiovasc Disord 2016 May;16:118. Vivo Radionuclide Generators for Diagnostics and against cancer: synergy supersedes singularity. J, Trøseid M, Nielsen SD. Marker of endothelial (FET) PET/MRI: feasibility, agreement and initial lymph node-negative patients with penile cancer Christensen TE, Bang LE, Holmvang L, Skovgaard Therapy. Bioinorg chem appl 2016; 2016:6148357. Editorial in Eur J Nucl Med Mol Imaging. 2016 dysfunction asymmetric dimethylarginine is experience. Eur J Nucl Med Mol Imaging 2016 - a national study from Denmark. BJU Int. 2016 DC, Oturai DB, Søholm H, Thomsen JH, Elmelund M, Oturai PS, Toson B, Biering-Sørensen Sep;43(10):1749-52. elevated in HIV infection but not associated with Jan;43(1):103–12. Jul;118(1):102-11. Andersson HB, Ghotbi AA, Ihlemann N, Kjaer A, F. Forty-five-year follow-up on the renal function Fliedner FP, Hansen AE, Jorgensen JT, Kjaer A. sub-clinical atherosclerosis. Journal of acquired Herth MM, Petersen IN, Hansen HD, Hansen Jee Hartmann Rasmussen L, Knudsen A, Katzenstein Hasbak P. 123I-MIBG scintigraphy in the subacute after spinal cord injury. Spinal Cord 2016 The use of matrigel has no influence on tumor immune deficiency syndromes (1999). 2016 M, Ettrup, Jensen AA, Lehel S, Dyssegaard A, TL, Gerstoft J, Obel N, Jørgensen NR, Kronborg state of takotsubo cardiomyopathy. JAAC Jun;54(6):445-51. development or PET imaging in FaDu human dec;73(5). Gillings N, Knudsen GM, Kristensen JL. Synthesis G, Benfield T, Kjaer A, Eugen-Olsen J, Lebech AM. 18 Cardiovasc Imaging. 2016 Aug;9(8):982-990. Engelholm LH, Melander MC, Hald A, Persson M, head and neck cancer xenografts. BMC medical Hansen AE, Andersen FL, Henriksen ST, Vignaud and evaluation of F-labeled 5-HT2A receptor Soluble urokinase plasminogen activator receptor Christiansen CB, Berg RMG, Plovsing R, Ronit A, Madsen DH, Jürgensen HJ, Johansson K, Nielsen imaging. 2016;16(1):5. A, Ardenkjaer-Larsen JH, Højgaard L, Kjaer agonists as PET ligands. Nucl Med Biol 2016 (suPAR) is a novel, independent predictive Holstein-Rathlou N-H, Yndgaard S et al. Dynamic C, Noerregaard KS, Ingvarsen SZ, Kjaer A, Trovik Frellsen AF, Hansen AE, Jølck RI, Kempen PJ, A, Klausen TL. Simultaneous PET/MRI with Aug;43(8):455-462. marker of myocardial infarction in HIV-1-infected Cerebral Autoregulation after Cardiopulmonary CS, Laerum OD, Bugge TH, Eide J, Behrendt Severin GW, Rasmussen PH, Kjaer A, Jensen 13C magnetic resonance spectroscopic imaging Hougaard A, Amin FM, Arngrim N, Vlachou M, patients: a nested case-control study. HIV Bypass. Thoracic and Cardiovascular Surgeon. N. Targeting a novel bone degrading pathway AT, Andresen TL. Mouse positron emission (hyperPET): phantom-based evaluation of PET Larsen VA, Larsson HB, Ashina M. Sensory medicine. 2016 maj;17(5):350-357. 2016;64(7):569-74. in primary bone cancer by inactivation of the tomography study of the biodistrubition of gold quantification. EJNMMI Physics; 2016;3(1):7. migraine aura is not associated with structural Johnbeck CB, Knigge U, Langer SW, Loft A, Cramer SP, Modvig S, Simonsen HJ, Frederiksen JL, collagen receptor uPARAP7Endo 180. J Pathol. nanoparticles with different surface coatings Hansen AF, Jensen MR, Nordholm-Carstensen A. grey matter abnormalities. Neuroimage Clin. Berthelsen AK, Federspiel B, Binderup T, Kjaer A, Larsson HB. Permabilty of the blood-brain barrier 2016 Jan;238(1):120-33. using embedded Copper-64. ACS Nano. 2016 Positron emission tomography/computed 2016;11:322-327. Prognostic value of 18F-FLT PET in patients with predicts conversion from optic neuritis to multiple Engelund Luna I, Monrad N, Binderup T, Thøgersen Nov;10(11):9887-9898. tomography in follow-up programmes for patients Højgaard L et al. Advice for 2018-2020 of the neuroendocrine neoplasms: A prospective head- sclerosis. Brain 2016 Sep;138(Pt 9):2571-83. CCB, Hilsted L, Jensen CV, Holstein-Rathlou Fuchs AM, Bang LE, Holmvang L, Hasbak P, Kjaer A, with colorectal cancer. Ugeskr Laeger. 2016 sep; Horizon 2020 Advisory Group for Societal to-head comparison with 18F-FDG PET and Ki67 in Cucchi F, Berg RM, Mortensen J. The alveolar- NH, Møller K. Somatostatin Immunoreactive Christensen TE. Takotsubo cardiomyopathy is an 178(37). Challenge 1, “Health, Demographic Change and 100 patients. J.Nucl.Med. 2016 Dec;57(12):1851- arterial oxygen difference in acute pulmonary Pancreatico-Duodenal Neuroendocrine Neoplasms acute cardiac syndrome induced by stress. Ugeskr Hasbak P, Enevoldsen LH, Fosbøl MØ, Skovgaard Well-being”. European Commission, 2016. 1857. thromboembolism: a classical concept revisited. Twenty-three cases evaluated according to the Laeger. 2016 Jun;178 (24):2-5. D, Knigge UP, Kjær A. Rubidium-82 uptake in Højgaard L, Hansen JR. Forskningssamarbejde og Johansen MD, Rochat P, Law I, Scheie D, Poulsen Scand J Clin Lab Invest. 2016 Oct;76(6):511-2. WHO 2010 Classification. Neuroendocrinology. Girard R, Fam MD, Zeineddine HA, Tan H, Mikati AG, metastases from neuroendocrine tumors: No fremtiden – Teoretisk fysik og moderne medicin. HS, Muhic A. Presentation of Two Cases with Denholt C, Gillings N. 99mTc-aprotinin – optimization 2016;103(5):567-77. Shi C, Jesselson M, Shenkar R, Wu M, Cao Y, Hobson flow response to adenosine. J Nucl Cardiol. 2016 Chapter in Fysikkens Filosofi, Informations Forlag. Early Extracranial Metastases from Glioblastoma and validation of radiolabelling kits for Ettrup A, Svarer C, McMahon B, da Cunha-Bang S, N, Larsson HB, Christoforidis GA, Awad IA. Vascular Aug;23(4):840-2. 2016;435-440. and Review of the Literature. Case Rep Oncol routine preparation for diagnostic imaging of Lehel S, Møller K, Dyssegaard A, Ganz M, Beliveau permeability and iron deposition biomarkers Henriksen OM, Larsen VA, Muhic A, Hansen AE, Hutchings M, Loft A, El-Galaly TC. PET/CT for HL Med. 2016;2016:8190950. amyloidosis. J Label Compd Radiopharm 2016 V, Jørgensen LM, Gillings N, Knudsen GM. Serotonin in longitudinal follow-up of cerebral cavernous Larsson HB, Poulsen HS, Law I. Simultaneous staging. I Gallamini A, red., PET Scan in Hodgkin Jorgensen JT, Norregaard K, Tian P, Bendix PM, Apr;59(4) 171-174. 2A receptor agonist binding in the human brain malformations. J Neurosurg. 2016 Aug 5:1-9. evaluation of brain tumour metabolism, structure Lymphoma. Springer. 2016:1-13 Kjaer A, Oddershede LB. Single Particle and PET-

62 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 63 Publications

based Platform for Identifying Optimal Plasmonic Knudsen AW, Krag A, Nordgaard-Lassen I, Langhans L, Klausen TL, Tvedskov TF, Vejborg I, Leth-Petersen S, Gabel-Jensen C, Gillings N, Lehel J, steering committee of the iPower study. Coronary availability in schizophrenia patients before and Nano-Heaters for Photothermal Cancer Therapy. Frandsen E, Tofteng F, Mortensen C, Becker U. Kroman N, Hesse B. Radioguided Surgery for S, Hansen DM, Knudsen GM, Kristensen JL. microvascular function and myocardial fibrosis after their first antipsychotic treatment: Relation Sci Rep. 2016;6:30076. Effect of paracentesis on metabolic activity in Localization of Nonpalpable Breast Lesions A Metabolic fate of hallucinogenic NBOMes. Chem in women angina pectoris and no obstructive to cognitive functions and psychopathology. Int J Juhl K, Christensen A, Persson M, Ploug M, Kjær A. patients with advanced cirrhosis and ascites. Mini-Review. Current Radiopharmaceuticals. Res Toxicol 2016 Jan;29(1):96-100. coronary artery disease: the iPower study. J Neuropsychopharmacol. 2016 Apr;19 (5):(10pages). Peptide-Based Optical uPAR Imaging for Surgery: Scand J Gastroenterol. 2016 May;51(5):601-9. 2016;9(2):114-20. Li F, Jorgensen JT, Forman J, Hansen AE, Kjaer A. Cardiovasc Magn Reson. 2016 Nov;18(1):76. Oberg K, Krenning E, Sundin A, Bodei L, Kidd M, In Vivo Testing of ICG-Glu-Glu-AE105. PLoS One Krakauer M, Kjaer A, Bennedbæk FN. 18F-FET-PET Lauritsen J, Kier MGG, Bandak M, Mortensen 64Cu-ATSM Reflects pO2 Levels in Human Head Nedergaard MK, Michaelsen SR, Perryman L, Tesselaar M, Ambrosini V, Baum RP, Kulke M, Pavel 2016 Feb; 11(2):15. in primary hyperparathyroidism: A pilot study. MS, Thomsen FB, Mortensen J, Daugaard G. and Neck Cancer Xenografts but Not in Colorectal Erler J, Poulsen HS, Stockhausen MT, Lassen M, Cwikla J, Drozdov I, Falconi M, Fazio N, Frilling Keller SH, Jakoby B, Svalling S, Kjaer A, Højgaard Diagnostics (basel). 2016 Aug;6(3):30. Pulmonary Function in Patients With Germ Cell Cancer Xenografts: Comparison with 64CuCl2. J U, Kjaer A. Comparison of 18F-FET and 18F-FLT A, Jensen R, Koopmans K, Korse T, Kwekkeboom L, Klausen TL. Cross-calibration of the Kriegbaum MC, Jacobsen B, Füchtbauer A, Hansen Cancer Treated With Bleomycin, Etoposide, and Nucl Med. 2016;57(3):437-43. small animal PET for the assessment of anti- D, Maecke H, Paganelli G, Salazar R, Severi S, Siemens mMR: easily acquired accurate PET GH, Christensen IJ, Rundsten CF, Persson M, Cisplatin. Journal of Clinical Oncology: Official Loft A, Khong PL, Borgwardt L, Berthelsen AK, VEGF treatment resonse in an orthotopic Strosberg J, Prasad V, Scarpa A, Grossman A, phantom measurements, long-term stability Engelholm LH, Madsen AN, Di Meo I, Lund IK, Journal of the American Society of Clinical Højgaard L. Pediatric whole-body oncology. model of glioblastoma. Nucl Med Biol. 2016 Walenkamp A, Cives M, Virgolini I, Kjaer A, Modlin and reproducibility. EJNMMI Physics. 2016 Holst B, Kjaer A, Lærum OD, Füchtbauer EM, Oncology. 2016 maj 1;34(13): 1492-9. Molecular Anatomic Imaging: PET/CT, PET/MR Mar;43(3):198-205. IM. A Delphic consensus assessment: imaging and Dec;3(1):1-8. Ploug M. C4.4A gene ablation is compatible Laursen HR, Henningsson S, Macoveanu J, Jernigan and SPECT CT. 3rd edition. Wolters Kluwer Nielsen CH, Erlandsson M, Jeppesen TE, Jensen biomarkers in gastropancreatic neuroendocrine Kjaer A, Torigian DA. Clinical PET/MR imaging in with normal epidermal development and TL, Siebner HR, Holst KK, Skimminge A, Knudsen 2016:653-659. MM, Kristensen LK, Madsen J, Petersen LC, Kjaer tumor disease management. Endocr Connect. 2016 oncology: Future perspectives. PET Clin. 2016 causes modest overt phenotypes. Sci Rep. 2016 GM, Ramzøy TZ, Erritzoe D. Serotonergic Mandeville JB, Sander CY, Wey HY, Hooker JM, A. Quantitative PET Imaging of Tissue Factor Seo;5(5):174-187. Oct;11(4): 489-493. May;6:25833. neurotransmission in emotional processing: Hansen HD, Svarer C, Knudsen GM, Rosen BR. Expression Using 18F-Labeled Active Site-Inhibited Olsen FJ, Bertelsen L, de Knegt MC, Christensen Klausen TL, Holm S. Nuklearmedicin – PET og la Cour JL, Andersen UB, Sørensen CH, Nygaard B, New evidence from long-term recreational poly- A regularized full reference tissue model for PET Factor VII. J Nucl Med. 2016 Jan;57(1):89-95. TE, Vejlstrup N, Svendsen JH, Jensen JS, Biering- nye sporstoffer. KVANT, Tidsskrift for Fysik og Jensen LT. Radioiodine Therapy Does Not Change drug ecstasy use. J Psychopharmacol. 2016 neuroreceptor mapping. Neuroimage. 2016 Jun Nielsen CH, Jeppesen TE, Kristensen LK, Jensen MM, Sørensen T. Multimodality Cardiac Imaging for Astronomi 2016;27:23-27. the Atherosclerotic Burden of the Carotid Arteries. Dec;30(12):1296-1304 27;139:405-414 El Ali HH, Madsen J, Wiinberg B, Petersen LC, the Assessment of Left Atrial Function and the Knudsen A, Christensen TE, Thorsteinsson K, Ghotbi Thyroid. 2016 Jul;26(7):965-71. Laursen J, Lundby T, Danielsen AK, Rosenberg J. Mc Mahon B, Andersen SB, Madsen MK, Hjordt LV, Kjaer A. PET Imaging of Tissue Factor in Pancreatic Association With Atrial Arrhythmias. Circulation: AA, Hasbak P, Lebech AM, Nielsen SD, Hov JR, Ladefoged CN, Law I, Anazodo U, Lawrence KS, Being a Fellow patient to a critically ill patient Hageman I, Dam H, Svarer C, da Cunha-Bang S, Cancer Using 64Cu-Labeled Active Site-Inhibited Cardiovascular Imaging. 2016 okt;9(10):e004947. Berge R, Ripa RS, Kjær A, Trøseid M. Microbiota- Izquierdo-Garcia D, Catana C, Burgos N, Cardoso leads to feelings of anxiety - an interview study. Baaré W, Madsen J, Hasholt L, Holst K, Frokjaer VG, Factor VII. J Nucl Med. 2016 Jul;57(7):1112-9. Olsen IH, Langer SW, Federspiel BH, Oxbøl J, Loft A, Dependent Marker TMAO is Not Associated With MJ, Ourselin S, Hutton B, Mérida I, Costes N, The Australian Journal of Advanced Nursing Knudsen GM. Seasonal difference in brain serotonin Nielsen MØ, Rostrup E, Wulff S, Glenthøj B, Ebdrup Berthelsen AK, Mortensen J, Oturai P, Knigge U, Decreased Myocardial Perfusion in Well-Treated Hammers A, Benoit D, Holm S, Juttukonda M, (Online). 2016;34(2):37-44. transporter binding predicts symptom severity in BH. Striatal reward activity and antipsychotic- Kjær A. 68Ga-DOTATOC PET and gene expression HIV-Infected Patients as Assessed by 82Rubidium An H, Cabello J, Lukas M, Nekolla S, Ziegler S, Law I. Integrated imaging in brain tumours. In: patients with seasonal affective disorder. Brain: A associated weight change in patients with profile in patients with neuroendocrine carcinomas: PET/CT. J Acquir Immune Defic Syndr. 2016 Aug Fenchel M, Jakoby B, Casey ME, Benzinger T, Hodler J, Kubik-Huch RA, von Schulthess GK, Journal of Neurology. 2016 May;139:1605-1614. schizophrenia undergoing initial treatment. JAMA strong correlation between PET tracer uptake and 1;72(4):e83-5. Højgaard L, Hansen AE, Andersen FL. A multi- editors. Diseases of the brain, head & neck. Moller S, Law I, Munck Af Rosenschold P, Costa Psychiatry. 2016 Feb;73(2):121-8. gene expression of somatostatin receptor subtype 2. Knudsen GM, Jensen PS, Erritzoe D, Baaré WFC, centre evaluation of eleven clinically feasible Diagnostic imaging and interventional techniques. J, Poulsen HS, Engelholm SA, Engelholm S. Nygård L, Vogelius IR, Fischer BM, Klausen TL, Am J Nucl Med Mol Imaging 2016 Jan;6(1):59-72. Ettrup A, Fisher PM, Gillings N, Hansen DM, brain PET/MRI attenuation correction techniques Zürich: Springer; 2016. p. 223-232. Prognostic value of 18F-FET PET imaging in re- Langer SW, Lonsdale MN, Persson GF, Bentzen Olsen RH, Pedersen LR, Snoer M, Christensen Hansen, LK, Hasselbalch SG, Henningsson S, Herth using a large cohort of patients. Neuroimage. Lehnert P, Møller CH, Mortensen J, Kjaergaard irradiation of high-grade glioma: Results of a phase S. Early lesion-specific18 F-FDG PET response to TE, Ghotbi AA, Hasbak P, Kjaer A, Haugaard SB MM, Holst KK, Iversen P, Kessing LV, Macoveanu J, 2016 Dec;147:346-359. J, Olsen PS, Carlsen J. Surgical embolectomy I clinical trial. Radiotherapy and Oncology: Journal chemotherapy predicts time to lesion progression Prescott E. Coronary flow velocity reserve by Madsen KS, Mortensen EL, Nielsen FA, Paulson OB, Langhans L, Klausen TL, Tvedskov TF, Talman ML, compared to thrombolysis in acute pulmonary of the European Society for Therapeutic Radiology in locally advanced non-small cell lung cancer. echocardiography: feasibility, reproducibility and Siebner HR, Stenbæk DS, Svarer C, Jernigan TL, Oturai PS, Vejborg I, Kroman N, Hesse B. embolism: morbidity and mortality. European and Oncology. 2016 okt;121(1):132-137. Radiother Oncol. 2016 Mar;118(3):460-4​. agreement with PET in overweight and obese Strother SC, Frokjaer VG. The Center for Integrated Preparation and Administration of 125I Labeled Journal of Cardio-thoracic Surgery: Official Mygind ND, Michelsen MM, Pena A, Frestad D, Nørbak-Emig H, Ebdrup BH, Fagerlund B, Svarer C, patients with stable and revascularized coronary Molecular Brain Imaging (Cimbi) Database. Seeds for Localization of Nonpalpable Breast Journal of the European Association for Cardio- Christensen TE, Ghotbi AA, Dose N, Faber R, Rasmussen H, Friberg L, Allerup PN, Rostrup E, artery disease. Cardiovasc Ultrasound. 2016 NeuroImage 2016 Jan;124(Pt B):1213-9. Lesions. Curr Radiopharm. 2016;9(2):143-9. thoracic Surgery. 2016 feb 1;51(2):354-361 Vejlstrup N, Hasbak P, Kjaer A, Prescott E, Kastrup Pinborg LH, Glenthøj BY. Frontal D2/3 receptor Jun;14(1):22.

64 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 65 Publications

Pedersen M, Karlsen MA, Ankjærgaard KL, Jensen Petersen AL, Henriksen JR, Binderup T, Elema painting with concomitant cisplatin in head years after treatment for hypersensitivity texture. Alzheimer’s Disease Neuroimaging microcirculatory function in type 2 diabetic LT. Primary hyperaldosteronism diagnosed with DR, Rasmussen PH, Hag AM, kjaer A, Andresen and neck cancer. Radiother Oncol. 2016 pneumonitis during childhood. Pediatric Initiative and the Australian Imaging Biomarkers patients. Diabetes 2016 Oct;65(10):3129-38 adrenal vein sampling. Characteristics and TL. In vivo evaluation of PEGylated 64Cu- Jul;120(1):76-80. Pulmonology. 2016;51(8):830-7. and Lifestyle Flagship Study of Ageing. Hum Brain Von Scholten BJ, Hasbak P, Christensen TE, Ghotbi follow-up after adrenalectomy in a Danish study. liposomes with theranostic and radiotherapeutic Rasmusen, T, Follin, B, Kastrup, J, Brandt-Larsen, Skovgaard D, Persson M, Kjaer A. PET imaging of Mapp. 2016 Mar;37(3):1148-61. AA, Kjaer A, Rossing P, Hansen TW. Cardiac 82Rb Scandinavian Journal of Clinical & Laboratory potential using micro PET/CT. European journal M, Madsen, J, Christensen, TE, Hammelev, K.P, urokinase-type plasminogen activator receptor Tabaksblat EM, Langer SW, Knigge U, Grønbæk PET/CT for fast and non-invasive assessment Investigation. 2016 feb;76(1):45-50. of nuclear medicine and molecular imaging. Hasbak, P, Kjaer, A. Angiogenesis PET tracer (uPAR) in prostate cancer: current status H, Mortensen J, Petersen RH, Federspiel of microvascular function and structure in 68 Pedersen NJ, Jensen DH, Hedbäck N, Frendø M, 2016;43(5):941-52 uptake ( Ga-NOADGA-E[cRGDyK]2) in induced and future perspectives. Clin Transl Imaging. BH, Ladekarl M. Diagnosis and treatment of asymptomic patients with type 2 diabetes. Kiss K, Lelkaitis G, Mortensen J, Christensen A, Petersen IN, Villadsen J, Hansen HD, Jensen AA, myocardial infarction in minipigs. Diagnostics. 2016;4(6):457-65. bronchopulmonary neuroendocrine tumours: Diabetologia. 2016 Feb;59(2):371-8. Specht L, von Buchwald C. Staging of early lymph Lehel S, Gillings N, Herth MM, Knudsen GM, 2016 Jun;6(2):26-29. Staberg M, Michaelsen SR, Stobbe Olsen ML, State of the art. Acta oncologica (Stockholm, Von Scholten BJ, Rosendahl A, Hasbak P, Bergholdt R, node metastases with the sentinel lymph node Kristensen JL. Convergent 18F-labeling and Rasmussen T, Follin B, Kastrup J, Christensen TE, Nedergaard MK, Villingshøj M, Stockhausen MT, Sweden). 2016 jan;55(1):3-14. Kjaer A, Rossing P, Hansen TW. Impaired coronary technique and predictive factors in T1/T2 oral evaluation of N-benzyl-phenethylamines as Hammelev KP, Kjær A, Hasbak P. Myocardial Hamerlik P, Poulsen HS. Combined EGFR- and Teuho J, Johansson J, Linden J, Hansen AE, Holm microcirculation in type 2 diabetic patients is

cavity cancer: A retrospective single-center study. 5-HT2A receptor PET ligands in the pig brain. perfusion of infarcted and normal myocardium in notch inhibition display additive inhibitory effect S, Keller SH, Delso G, Veit-Haibach P, Magota associated with elevated circulating regulatory T Head & Neck 2016 Apr;38 Suppl 1:E1033-40. Bioorg Med Chem 2016 Nov;24(12):5353-5356. propofol-anesthesized minipigs using 82Rubidium on glioblastoma cell viability and glioblastoma- K, Saunavaara V, Tolvanen T, Teras M, Iida H. cells and reduced number of IL-21R(+) T cells. Pérez-Medina C, Binderup T, Lobatto ME, Tang Qayyum AA, Qayyum F, Larsson HB Kjaer A, Hasbak PET. J Nucl Cardiol. 2016 Jun;23(3):599-603. induced endothelial cell sprouting in vitro. Effect of Attenuation Correction on Regional Cardiovasc Diabetol 2016 Apr;15:67. J, Calcagno C, Giesen L, WesselCH, Witjes J, P, Vejlstrup NG, Kastrup J. Comparison of rest Ripa RS, Pedersen SF, Kjær A. PET/MR Imaging Cancer Cell Int. 2016 Apr 26;16:34 Quantification Between PET/MR and PET/CT: A Warberg J, Kjaer A. Humanbiology – a textbook Ishino S, Baxter S, Zhao Y, Ramachandran S, and adenosine stress quantitative and semi- in Vascular Disease: Atherosclerosis and Stenbæk DS, Fisher PM, Budtz-Jørgensen E, Pinborg Multicenter Study Using a 3-Dimensional Brain (Danish), 1st edition 2016, 536 pages, Polyteknisk Eldib M, Sánchez-GaytánBL, Robson PM, Bini J, quantitative myocardial perfusion using magnetic Inflammation. PET Clin. 2016 Oct;11(4):479-88. A, Hjordt LV, Jensen PS, Knudsen GM, Frokjaer Phantom. J Nucl Med 2016;57(5):818–24. Forlag, Copenhagen, Denmark. ISBN 978-87-502- Granada JF, Fish KM, Stroes ES, Duivenvoorden resonance in patients with ischemic heart disease. Ronita A, Haissman J, Kirkegaard-Klitbo DM, VG. Sex hormone manipulation slows reaction Tønnesen R, Hovind P, Jensen LT, Schwarz P. 1111-2. R, Tsimikas S, Lewis JS, Reiner T, Fuster V, Kjaer Clin Imaging. 2016;41:149-156. Kristensen TS, Lebech AM, Benfield T, Gerstoft time and increases labile mood in healthy women. Determinants of vitamin D status in young adults: Wille MM, Dirksen A, Ashraf H, Saghir Z, Bach KS, A, Fisher EA, Fayad ZA, Mulder WJ. In Vivo Rajan S, Wissenberg M, Folke F, Hansen SM, Gerds TA, J, Ullum H, Køber J, Kjaer A, Kofoed K, Vestbo Psychoneuroendocrinology. 2016 Jun;68:39-46 influence of lifestyle, sociodemographic and Brodersen J, Clementsen PF, Hansen H, Larsen PET Imaging of HDL in Multiple Atherosclerosis Kragholm K, Hansen CM, Karlsson L, Lippert FK, J, Nordestgaard B, Lundgren J, Nielsen SD. Sun Y, Ma X, Zhang Z, Sun Z, Z Xiaodong, Loft M, anthropometric factors. BMC Public Health. 2016 KR, Mortensen J, Rasmussen JF, Seersholm N, Models. JACC Cardiovasc Imaging 2016 Køber L, Gislason GH, Torp-Pedersen C. Association Copenhagen comorbidity in HIV infevtion Bingbing D, Liu C, Xu L, Yang M, Jiang Y, Cheng May 11;16(1):385. Skov BG, Thomsen LH, Tønnesen P, Pedersen JH. Aug;9(8):950-961. of Bystander Cardiopulmonary Resuscitation and (COCOMO) study: a study protocol for a Z, Hong X. Preclinical Study on GRPR-Targeted Tønnesen R, Schwarz P, Hovind P, Jensen LT. Results of the Randomized Danish Lung Cancer Persson GF, Scherman Rydhög J, Josipovic M, Survival According to Ambulance Response-times longitudinal, non-interventional assessment 68Ga-Probes for PET Imaging of Prostate Cancer. Physical exercise associated with improved Screening Trial with Focus on High-risk Profiling. Maraldo MV, Nygård L, Costa J, Berthelsen AK, after Out-of-Hospital Cardiac Arrest. Circulation of non-AIDS comorbidity in HIV infection in Bioconjugate Chem. United States. 2016 BMD independently of sex and vitamin D levels American journal of respiratory and critical care Specht L, Aznar MC. Deep inspiration breath-hold (Baltimore). 2016 nov 22;134(22):2095-2104 Denmark. BMC Infect Dis. 2016 Nov;16(1):713. Aug;27(8):1857–64. in young adults. Eur J Appl Physiol. 2016 medicine. 2016;193(5):542-551. volumetric modulated arc radiotherapy decreases Rasmussen H, Frokjaer VG, Hilker RW, Madsen Shaw R, Christensen A, Java K, Maddani RE, Sundstrup E, Jakobsen MD, Andersen LL, Andersen Jul;116(7):1297-304. Zwan MD, Rinne JO, Hasselbalch SG, Nordberg A, dose to mediastinal structures in locally advanced J, Anhøj S, Oranje B, Pinborg LH, Glenthøj B, Liloglou T, Asterios T, von Buchwald C, Wessel TR, Randers MB, Helge JW, Suetta C, Schmidt JF, Vestergaard MB, Lindberg U, Aachmann-Andersen Lleo A, Herukka SK, Soininen H, Law I, Bahl JM, lung cancer. Acta oncologica (Stockholm, Knudsen GM. Low frontal serotonin 2A receptor I, Kiss K, Kjaer A, Lelkaitis G, Long A, Risk J, Bangsbo J, Krustrup P, Aagaard P. Positive NJ, Lisbjerg K, Christensen SJ, Law I, Rasmussen Carter SF, Fortea J, Blesa R, Teunissen CE, Bouwman Sweden). 2016 aug;55(8):1053-6. binding is a state marker for schizophrenia? Journal Robinson M: Intraoperative Sentinel Lymph effects of 1-year football and strength training P, Olsen NV, Larsson HB. Acute hypoxia increases FH, van Berckel BN, Visser PJ. Use of amyloid- Persson M, Nedergaard MK, Brandt-Larsen M, of European College of Neuropsychopharmacology. Node Evaluation: Implications of Cytokeratin on mechanical muscle function and functional the cerebral metabolic rate – a magnetic PET to determine cutpoints for CSF markers: A Skovgaard D, Jørgensen JT, Michaelsen SR, 2016 Jul;26(7):1248-50. 19 Expression for the Adoption of OSNA in Oral capacity in elderly men. Eur J Appl Physiol. 2016 resonance imaging study. J Cereb Blood Flow multicenter study. Neurology. 2016;86(1):50-58. Madsen J, Lassen U, Poulsen HS, Kjaer A. Rasmussen JH, Håkansson K, Vogelius IR, Aznar Squamous Cell Carcinoma. Ann Surg Oncol. 2016 Jun;116(6):1127-38. Metab 2016;36(6):1046-1058. Østergaard ML, Ewertsen C, Konge L, Albrecht- Urokinase-type plasminogen activator receptor MC, Fischer BM, Friborg J, Loft A, Kristensen Nov;23(12):4042-4048. Sørensen L, Igel C, Liv Hansen N, Osler M, Lauritzen Von Scholten BJ, Hansen CS, Hasbak P, Kjaer A, Beste E, Bachmann Nielsen M. Simulation-Based as a potential PET biomarker in glioblastoma. J. CA, Bentzen SM, Specht L. Phase-1 trial of Sisman Y, Buchvald F, Blyme AK, Mortensen J, M, Rostrup E, Nielsen M; Early detection of Rossing P, Hansen TW. Cardiac autonomic Abdominal Ultrasound Training - A Systematic Nucl. Med. 2016, Feb, 57(2), 272-8. 18F-Fluordeoxyglucose based radiation dose Nielsen KG. Pulmonary function and fitness Alzheimer’s disease using MRI hippocampal function is associated with the coronary Review. Ultraschall Med. 2016 Jun;37(3):253-61.

66 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 67 Research

Andreas Kjær

Research and development is a key activity and New tracers promising new PET tracers in our developmental focus area of our department. We have over the An array of projects that are aimed at develop- pipeline and expect several of these to be trans- years build, and continuously strengthened, a ment of new PET and SPECT tracers for non- lated into clinical use within the next years. comprehensive research program with focus invasive tissue characterization, phenotyping, on developing innovative solutions to solve are currently undertaken. Within cancer, but unmet needs in patients. We constantly adjust not limited to this, these novel tracers are to be PET/MRI our research program to be clinically relevant used for diagnosing, staging, risk stratification As one of the first departments that had a hybrid and timely. Our research program is built on and therapy planning and monitoring. Two re- PET/MRI scanner installed, we have continuous- established strong in-house competencies com- cent examples of tracers that were both taken ly expanded our research program on PET/MRI bined with strategic collaborations with leading first-in-humans by us during 2016 are with particular attention on the added value of 68 68 international and national research groups with Ga-NOTA-AE105 and Ga-NODAGA-RGD2. The combining PET and MRI. We currently undertake complementary expertise. Our research program first tracer,68 Ga-NOTA-AE105, is a marker of a substantial number of clinical trials with the focuses in particular on development of new cancer aggressiveness and metastatic potential purpose to fully unfold the potential of PET/MRI tracers for PET, PET/MRI hybrid imaging, thera- (the invasive phenotype). The second tracer, by combining molecular imaging with PET and 68 nostics, clinical evaluation of new diagnostic Ga-NODAGA-RGD2, is visualizing neoangio- multiparametric MRI. In addition, we develop methods, and on the use of methods from clini- genesis, which is the target for anti-angiogenesis new methods for PET/MRI. The goal is to improve cal physiology and nuclear medicine to study drugs such as bevazizumab (Avastin®). As part tissue characterization and response monitoring pathophysiology. Translational research in mo- of our research program, we developed a com- ability in cancer treatment, paediatric studies, brain lecular imaging is given special attention in or- prehensive platform for validation of new tracers studies and atherosclerotic plaque characteriza- der to accelerate translation of new tracers into including cell laboratory, molecular biology (pro- tion. Focus of MRI includes the use of diffusion clinical use in patients. Current major research teomics and genomics), histology and biomark- weighted images (DWI)/apparent diffusion coeffi- areas are briefly described below er laboratory. We currently have several other cient (ADC) and magnetic resonance spectroscopy

68 department of clinical physiology, nuclear medicine & pet 7 Research Figure showing first-in-humans uPAR-PET/CT in breast cancer patient using the PET tracer 68Ga-NOTA-AE105. In addition to the primary tumour being clearly visualized, an axillary metastasis was shown. Traditional work-up with chest X-ray and ultrasonography did not visualize any metastases. Pathology confirmed that the uPAR positive lymph node contained metastatic breast cancer tissue (from Skovgaard et al. J Nucl Med 2016)

3 Figure showing head-to-head comparison of our in-house developed somatostatin receptor imaging ligand 64Cu- DOTATATE with 68Ga-DOTATOC. In this patient the higher sensitivity of 64Cu-DOTATATE is demonstrated as a bone metastasis is clearly seen on 64Cu-DOTATATE-PET (middle panel) but not on 68Ga-DOTATOC-PET (upper panel). At follow-up 18 months later the metastasis could also be seen on 68Ga-DOTATOC-PET (from Bardram et al. J Nucl Med 2016).

(MRS). With access also to preclinical PET and ways is reflected in glucose utilization and thereby the use of respiratory gating are also currently to imaging of dementia using various new tracers. MRI, we are capable of working translational FDG uptake. Currently, we combine 13C-pyruvate being evaluated. Many of these studies also now Brain tumours are in particular studied with the when developing and evaluating new methods. with non-FDG PET tracers as well as implement include PET/MRI to study the added value com- amino acid tracer FET but also with novel in-house As an example, the use of PET/MRI for radiation other 13C-compounds for MRSI. So far, our results pared to PET/CT. developed tracers as uPAR-targeting ligands. In co- therapy planning and response monitoring is be- seem to support that hyperPET may be superior operation with Neurobiology Research Unit and ing evaluated both preclinically and clinically. in cancer phenotyping and response monitoring Centre for Integrated Molecular Brain Imaging, and therefore has the potential to become a useful Paediatric nuclear medicine investigations neuroreceptor ligands have been developed and clinical modality. Also in the field of hyperPET our At the department we undertake many paediatric in- used for research in neurobiology. The focus has Hyperpolarized 13C-MRSI approach is translational. vestigations. Numerous research protocols with the mainly been on the serotonergic system. We were the first to install a dynamic nuclear po- use of PET and SPECT are carried out in coopera- larized (DNP) for hyperpolarization of 13C-labeled tion with clinical departments, particularly within compounds next to a PET/MRI scanner. According- Clinical PET/CT in oncology oncology and function of the hepato-biliary system. Functional MR ly, we have given particular attention to devel- We continuously carry out a large number of pro- The use of PET/MRI in children to save radiation Studies on functional brain MR are undertaken opment of and research in the combination of spective protocols for evaluation of the diagnos- dose is also the subject of several investigations. in close collaboration with clinical departments hyperpolarized 13C-MRS and PET and the added tic and prognostic value of PET/CT with various including neurology and psychiatry. Special value of combining the modalities, a technique we tracers, including the ones developed in-house, attention is given to development of new methods named hyperPET. We have so far studied the use in various forms of cancer both in children and in Neuro PET for functional MRI and clinical application of new of hyperPET in tissue characterization in cancer, adults. Head-to-head comparison studies of new With the use of PET/MR, PET/CT including HRRT functional and molecular MR methods. Methods cardiovascular disease and inflammation/infec- PET tracers and established imaging methods are PET, studies on brain tumours are undertaken. are targeted at obtaining information on tissue tion. Using 13C-pyruvate we have further studied also performed. The use of PET/CT for the plan- Studies of brain perfusion using PET or DCE-CT physiology, organ perfusion and molecular biology. the Warburg effect directly and how it is not al- ning of radiation therapy (“dose-painting”) and are also performed. In addition, attention is given

70 department of clinical physiology, nuclear medicine & pet Research

Atherosclerosis basis of this, screening algorithms for detection effect of exercise, immobilization and aging. In include neuroendocrine tumours, prostate cancer To be able to visualize non-invasively atheroscle- of ischaemic heart disease are evaluated. Some addition, data are collected on the same para- and ovarian cancer. Treatment with radionuclides rosis and predict vulnerability of atherosclerotic of the studies are combined with PET tracers meters from a population-based study. These data will in part be based on imaging using new tracers plaques, studies using PET/MRI and PET/CT are characterizing other aspects of the myocardium, will serve as a reference database and elucidate for molecular profiling or the same ligand as the undertaken. Patient groups at risk are studied its viability and regeneration. Several of the markers to predict ageing-related disease. therapy (theranostics) for better outcome and and special focus is on the value of new specific studies are performed using PET/MRI to obtain fewer side effects. The concept of a tracer that PET tracers, e.g. for the study of macrophage additional information. visualizes the target prior to starting therapy is activation and atherosclerosis-induced cell pro- Inflammation, infection and rejection also known as companion diagnostics. liferation in the bone marrow and spleen. The Non-invasive imaging of inflammation and in- ambition is to develop an image-based algorithm Lung studies fection is currently being undertaken in several for identification of patients at risk that will Numerous studies using lung function testing studies at the department. Also studies on the Image guided surgery benefit from surgery. As we were the first to and lung scintigraphy in different patient groups, best way to visualize and evaluate rejection reac- The concept of intraoperative guidance using publish data showing advantage of PET/MRI over e.g. lung transplantation and endobronchial tions are performed. In some studies, the added either radioactive or optical imaging ligands is PET/CT for carotid artery imaging we have con- stenting for emphysema, are undertaken. value of MR-derived parameters of PET/MR is increasingly used for surgery. In close collabora- tinued to develop vascular imaging using PET/MRI Accordingly, we recently demonstrated the value studied. The department is partner in the PERSI- tion with clinical departments we have recently with special focus on new PET tracers. of combined use of SPECT/CT for diagnosing MUNE program, personalized medicine of infec- developed one of our most promising PET ligands pulmonary embolism. The value of biomarkers tion complications in immune deficiency. Finally, targeting uPAR into an optical probe. This probe in combination with imaging is also studied. In on a translational basis development of new PET will be used for intraoperative delineation of Nuclear cardiology addition, evaluation of the different ventilation ligands for immune response monitoring is cur- cancer to ensure negative margins while leaving The ability to measure absolute myocardial per- tracers for assessment of ventilation inhomo- rently being pursued. normal tissue intact. The technology, which will fusion and myocardial flow reserve by means of geneity is undertaken. Research is also being be used in pair with preoperative PET imaging of 82Rb PET is exploited to study the regulation of conducted into mucociliary clearance, a method the same target, is particularly promising in concert these parameters in various cardiovascular disea- pioneered at the department, of the nose and Radionuclide treatment and theranostics with robotic surgery. ses and the predictive value of the measures, e.g. lungs. Finally, the department is participating in Targeted radionuclide therapy using beta- or final infarct size. Also the influence of interven- a large study colleting data for a lung function alpha-emitting specific ligands binding to certain tions including gene therapy, pharmacological test reference database. cancer characteristics has been undertaken for Whole body counting treatment and exercise may be closely monitored many years at the department. The department Whole body counting is used for precise measure- using 82Rb PET. In addition, with the use of takes part in research within this area by testing ments of body composition in a series of collabo- 123I-MIBG the cardiac sympathetic innervation Studies of muscle function new ligands and producing relevant isotopes. In rative studies. Also, studies on the absorption of and activity may be measured. With the use of Applying methods from clinical physiology and particular, we also in-house develop new thera- certain minerals from the gastrointestinal tract SPECT/CT or PET/CT the development of ischae- nuclear medicine as well as molecular analyses, nostics based on promising imaging ligands are undertaken. mic heart diseases is studied in selected groups muscle function, bone density and body com- labeled with beta or alpha emitting radionuclides. of patients, e.g. HIV and hepatitis patients. On position are studied. The current focus is on the Cancers that are currently being targeted clinically

72 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 73 74 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 75 Cluster for Molecular Imaging

Andreas Kjær

Implementation of precision medicine, i.e. tailor- high sensitivity, often they can be ing therapy to the disease characteristics of each micro-dosed. Finally, successful patient, has led to a need for diagnosing at the imaging ligands may be developed molecular level. Traditional molecular biology into radionuclide therapy, such methods use tissue sampling for in vitro analy- imaging-therapy pairs are known sis. In contrast, molecular imaging allows for as theranostics. whole-body non-invasive studies at the molecular level in intact organisms. A further advantage of Our molecular imaging and thera- image based techniques is circumvention of nostics research program is aimed sampling error, i.e. that a biopsy is not represen- at, through use of molecular biology tative of the whole disease due to heterogeneity. and imaging techniques in both animals and 1 It is possible to label almost any molecule with humans to develop, evaluate and use non-invasive Figure 1. The major steps involved in PET tracer radioactive isotopes suitable for PET imaging molecular imaging for human tissue characteri- development: following selection of the key-process and such molecular imaging PET ligands may zation. Major applications of these tracers are ex- involved in pathophysiology of a disease, a relevant then be used for visualization of tumour specific pected to be: 1) planning of individualized, molecular target is defined. Thereafter, a specific ligand receptors and tissue characteristics, e.g. tumour tailored therapy, 2) testing of new drug candidates is developed and labeled with a suitable radionuclide aggressiveness or angiogenesis. Especially within and 3) basis for development of radionuclide for imaging. Target validation (specificity) is then tested cancer biology, but not limited to this, the tech- therapy (theranostics). in relevant animal models and biodistribution studied nique is expected to lead to a break-through in for calculation of radiation dosimetry. Successful, lead candidates are then rigorously tested for possible toxicity diagnosing and treatment. Among available The development of new molecular imaging according to European guidelines. Following approval by molecular imaging methods, the nuclear medi- tracers for PET is a complex process that involves the health authorities a first-in-humans phase I clinical cine based technologies and in particular PET, many steps from definition of target to final use trial may then be initiated. If successful, phase II studies have the greatest translational potential as they of the tracer in patients. The major steps in- of clinical utility are then pursued. Imaging ligands can be directly transferred from animal models volved in PET tracer development and translation may also be used as a starting point for new targeted to use in humans. Also, due to the unsurpassed into patients are depicted in the figure 1. therapies, in particular radionuclide based therapies.

76 department of clinical physiology, nuclear medicine & pet 3 Figure 2. PET/MR imaging of human patient- derived (PDX) HER2 positive breast cancer implanted orthotopically into the brain of a mouse to be used as a model of breast cancer brain metastasis. For PET imaging, an in-house developed HER2 targeting tracer was used. The model can e.g. be used to evaluate whether new breast cancer therapies are also efficient in brain metastases (image provided by Carsten H. Nielsen)

3 Figure 3. Myocardial scintigraphy (99mTc-MIBI SPECT/CT) before (left panels) and after (right panels) induction Figure 6. Optical imaging of uPAR using our in-house developed of myocardial infarction in rats. One application of ICG:AE105 in orthotopic human xenograft mouse tumour model. Up- the model is testing the ability of new PET tracers to per panels: Close correlation ex vivo between immunohistochemistry identify area at risk and predict final infarct size (left) and fluorescence of ICG:AE105 (middle); Lower panels: uPAR (Image provided by Andreas Clemmensen). optical signal in orthotopic human pancreatic cancer (left) and glio- blastoma (middle). The image at right shows how the ligand is used to see whether all tumour tissue is resected – tumour tissue (bright) left behind at arrow (Images provided by Karina Juhl and Anders Christensen) Figure 5. Comparison of the different in vivo models used by us in the development and testing of new PET tracers and targeted radionuclide therapies

1 Through establishment in 2003 of Cluster for models using human cancer cell lines. Most Figure 4. Post myocardial infarction angiogenesis in dogs with spontaneous tumours scheduled for recently obtained approval for animal experiments Some tissue characteristics currently targeted Molecular Imaging at the Faculty of Health and recently, we also implemented the use of a minipig model. By using an in-house developed cancer therapy. The latter allows for testing in using alpha-emitting therapy. Also preclinical studies for imaging: 68 13 Medical Sciences, University of Copenhagen patient-derived tumours (PDX) for orthotopic angiogenesis PET tracer ( Ga-NODAGA-RGD2 ) “full-size” as well as evaluation of tumour-stroma in the field of hyperpolarized C-MRS and hyperPET 33 Cancer specific receptors (numerous projects, 82 (headed by Professor Andreas Kjær) a specialized implantation to even better mimic the conditions and the PET myocardial perfusion tracer Rb, it interaction due to the syngeneic tumour environ- are performed in collaboration with DTU. Finally, e.g. SST, HER2, EGFRvIII) was possible to visualize increased angiogenesis facility at the Panum Institute for molecular in cancer patients (Figure 2). ment. In this way we bridge between xenograft also optical imaging has gained translational 33 Glycolytic activity (PET and hyperpolarized in the area of infarction (yellow arrows; image imaging in animals with PET, SPECT, CT, MRI models and first-in-human studies. The relative potential as it can be used intraoperatively for MRSI) modified from Rasmussen et al. Diagnostics and optical imaging has been established. This Furthermore, we have also introduced and deve- (Basel) 2016) value and pros and cons of the different models delineation of tumours and in particular when 33 Cell proliferation has improved our translational capacity since we loped animal models of cardiovascular diseases in- are shown below in figure 5. robotic surgery is performed (Figure 6). 33 Amino acid transport are now able to test new tracers and radionuclide cluding atherosclerosis, myocardial infarction and 33 Hypoxia therapies in animal models prior to clinical use. takotsubo (Figure 3). For studies of atherosclerosis At Cluster for Molecular Imaging we always seek Currently the main focus of the translational re- 33 Apoptosis In accordance with this we have currently several also mini pigs and rabbits are used (Figure 4). to match our clinical methods to be able to develop search in tracers for non-invasive tissue charac- 33 Necrosis new tracers of our pipeline in pre-clinical testing new techniques for use in patients. Accordingly, terization is on the use in cancer and cardio- 33 Angiogenesis that already are or soon will become available for Over the last 10 years we have build a transla- we recently added SPECT/CT capabilities to our vascular disease and new targeted radionuclide 33 Invasive cancer phenotype human use. A strong focus has recently been on tional platform for development of new PET tracers existing PET/MRI/MRS capabilities. SPECT/CT therapies for cancer. However, we also perform 33 Atherosclerotic plaque vulnerability the use of more clinically relevant animal cancer in cancer. The platform includes, after testing in will in particular be used to visualize 177Lu-labeled studies within molecular imaging of inflamma- 33 Immune-response models, which include orthotopic human xeno- orthotopic human xenograft tumours in mice, radionuclide therapy ligands to investigate bio- tion and metabolism, e.g. activation of brown graft tumours as well as metastatic cancer early use of promising PET tracers in companion distribution and binding to tumours. In addition, we adipose tissue.

78 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 79 Collaboration with Landssygehuset, Faroe Islands

Jann Mortensen and Thomas Levin Klausen

The Faroe Islands population of 50,000 is served 360 scintigraphies of lungs, bones, thyroid, by 2 smaller hospitals in Klaksvík and Tvøroyri kidneys, sentinel nodes and renography in 2016 and the larger National Hospital of the Faroe on the department´s 2-headed Skylight camera. Islands, Landssjúkrahúsið in Tórshavn. Around 400 lung functions test were performed with the Jaeger whole body plethysmograph and The National hospital has a staff of 850 and 180 nearly 500 routine and research DXA studies were beds. The 8,000 in-patients and 60,000 out-pa- performed with The Norland DXA 840 scanner. tients annually are taken care of by 29 speciali- ties, of which 9 are via consultant collaborations, Second opinion on scintigraphies and lung func- including collaboration in clinical physiology tion measurements is provided via a direct tele- and nuclear medicine with our department at medicine connection. The responsible physician Rigshospitalet. and phycisist for Nuclear Medicine in Tórshavn is Consultant, DMSc Jann Mortensen and Physicist The Department of Clinical Physiology and Nu- Thomas Levin Klausen. clear Medicine in Tórshavn performed around

80 department of clinical physiology, nuclear medicine & pet department of clinical physiology, nuclear medicine & pet 81 CIMBI Center for Integrated Molecular Brain Imaging, University of Copenhagen, Rigshospitalet

We appreciate the excellent collaboration with Professor Gitte Moos Knudsen, Chair of the Neurobiology Research Unit at Rigshospitalet, University of Copenhagen and also Director of the CIMBI, Center for Integrated Molecular Brain Imaging.

The focus of the research program is neurobiology, physiology and pathophsiology, molecular imaging and neuroreceptor ligands with focus on the serotonergic system. https://cimbi.dk/

82 department of clinical physiology, nuclear medicine & pet MSc in Medicine and Technology

Liselotte Højgaard

In cooperation with the Technical University and we have numerous students working with of Denmark (DTU) and the University of bachelor and master reports in collaboration Copenhagen (KU), the Department represented with DTU, IMM (Institute for Mathematical by Professor Liselotte Højgaard is involved in Modelling), Professor Rasmus Larsen and DTU the MSc program in Medicine and Technology. Electro with Professor Jørgen Arendt Jensen. It is a five year bioengineering degree at bachelor and master level. The first masters graduated in A warm thank you to Professor Jørgen Arendt 2008. You can read more about the program at Jensen, Associate Professor Kaj-Åge Henneberg, www.medicin-ing.dk. Professor Jens E. Wilhjelm, DTU and Professor Tine Alkjær Eriksen, University of Copenhagen At present several of these bioengineers are for their great effort and our fine collaboration seconded to the department as PhD students, both on education and research.

84 department of clinical physiology, nuclear medicine & pet Danish National Research Foundation

Professor Liselotte Højgaard Chairman of the Board of the Danish National Research Foundation

The Danish National Research Foundation (DNRF) awarded a CoE through fierce competition involv- Foundation 3 bio DKK on the State Budget for is an independent organisation established by the ing a two-staging application process. The objec- 2015 to secure the Foundation to 2036. Danish Parliament in 1991 with the objective tive of the CoE program is to strengthen Danish to promote and stimulate basic research at the research by providing the best possible working Professor Liselotte Højgaard is Chair of the Board highest international level at the frontiers of all conditions and organizational setup for selected of the Danish National Research Foundation. scientific fields. The Foundation could celebrate top researchers. Centers may be established with- the first successful 25 years November 2016. The in or across all fields of research. A total of 100 The board members at the end of 2016: Center of Excellence (DoE) program is the main centers of Excellence have been established so far. Professor Liselotte Højgaard, Professor Eivind funding mechanism together with the Niels Bohr Hiis Hauge, Professor Eero Vuorio, Professor, professorships. Since 1991 the Foundation has In 2013 DNRF was evaluated by an international Dr. Bart De Moor, Professor Christina Moberg, commited itself to support Danish Research with panel leader by Dr Wilhelm Krull, Secretary Professor Morten Overgaard Ravn, Professor more than 6 billion DKK (= 800 mio €). General of Die Volkswagen Stiftung. The outcome Minik Rosing, Professor Jesper Ryberg and was very positive and showed that the DNRF’s Professor Anne Scott Sørensen. The Center of Excellence is the primary funding Centers of Excellence are on level with the very mechanism and the Foundation’s flagship. A best researchers in the world. The outcome was Professor Søren-Peter Olesen is Director of DNRF, center grant is large and flexible, and a center very positive, and a continuation of DNRF was and Steen Marcus is Vice Director. A warm thank 3 may have a lifetime up to 10 years. Only top re- recommended to the Danish Parliament and you to all staff members and directors for an Liselotte Højgaard searchers with the most ambitious ideas will be Government. The Danish Parliament gave the excellent collaboration. and Søren-Peter Olesen

86 department of clinical physiology, nuclear medicine & pet Editors Liselotte Højgaard Accreditation Vibeke Rønn Layout Eckardt ApS

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Photos Sophie Kalckar Joakim Rohde Mikkel Østergaard

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Copyright Department of Clinical Physiology, Nuclear Medicine & PET Rigshospitalet University of Copenhagen Blegdamsvej 9 DK 2100 Copenhagen Ø Denmark

Contact Rigshospitalet and our department have been accredited succesfully by: Professor Liselotte Højgaard E-mail: [email protected] 33 Center of Excellence by the European Neuroendocrine Tumor Society Phone: +45 3545 4215 33 Certified by SIS, National Institute of Radiation Protection, The Danish National Board of Health 33 Danish Medicines Agency 33 The Danish National Board of Health, MD Specialist education 33 EURATOM, The European Atomic Energy Community 33 Section of Nuclear Medicine of the European Union of Medical Specialists (UEMS) 33 Accreditation of Nuclear Medicine Training Centers Committee, MD Specialist Education 33 European Association of Nuclear Medicine 33 The Specialty Advisory Committee (SFR) in Clinical Physiology and Nuclear Medicine

88 department of clinical physiology, nuclear medicine & pet Department of Clinical Physiology, Nuclear Medicine & PET Rigshospitalet, KF Section 4011 Blegdamsvej 9 2100 Copenhagen Ø, Denmark Telephone: +45 3545 4011 Fax no: +45 3545 4015 Mail: [email protected]

Department of Clinical Physiology, Nuclear Medicine & PET Rigshospitalet, PET Section 3982 Blegdamsvej 9 2100 Copenhagen Ø, Denmark Telephone: +45 3545 3919 Fax no: +45 3545 3898 Mail: [email protected]

Department of Clinical Physiology, Nuclear Medicine & PET Rigshospitalet, Glostrup Section Nordre Ringvej 57 Entrance 1, 2nd floor 2600 Glostrup Telephone: +45 3863 2434 Fax no: +45 3863 3928 Mail: [email protected] www.rigshospitalet.dk/afdelinger-og-klinikker/ diagnostisk/klinik-for-klinisk-fysiologi-nuklearmedicin-og-pet