6Th Symposium on Medical Radioisotopes

BOOK OF ABSTRACTS SCK•CEN/22527775 SCK•CEN BA-0092

6th Symposium on Medical Radioisotopes

Challenges in production and transport and applications

in the presence of HRH Princess Astrid

Lamot Conference and Heritage Centre

Mechelen | May 11, 2017

SCK•CEN Boeretang 200 BE-2400 MOL Belgium http://www.sckcen.be

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BOOK OF ABSTRACTS SCK•CEN BA-0092

Scientific and organising committee

*member of the organising committee

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Contents

Introduction ...... 7 Programme ...... 8 Abstracts and biographies ...... 11

The new BR2 reactor - perspectives for radioisotope production The MYRRHA accelerator - perspectives for radioisotope production

World status on reactor and cyclotron radioisotope production Good Distribution Practice: challenges and implementation Security issues during transport and delivery

Urban mobility and Good Distribution Practice Safety and security: general vision by FANC & the upcoming transport regulations Central vs. distributed radiopharmacies The Ge/Ga generator: first evaluation

Safety/security issues in the hospital Theranostics Which radionuclide for solid tumour treatment? Degenerative neurological diseases

Posters ...... 41

Hybrid gold nanoparticles coated with organic polymers and antibodies as platform for cancer theranostics: Cytotoxicity assessment

213Bismuth-labeled nanobodies as a new treatment approach in Targeted Alpha Therapy

Producing 225Ac at CERN-MEDICIS via combined Resonant Laser Ionization and Mass Separation

Cyclotron produced terbium radionuclides for theranostic applications

Analysis of Laser Resonance Ionization of Lutetium for the MEDICIS project

Separation of radium and actinium from historical Th-229 sources for production of radioisotopes for targeted alpha immunotherapy

A type B container for the transport of isotopes for medical purpose: design’s strategies and shielding characterization

CERN-MEDICIS: A new facility for the production of innovative medical radioisotopes

Visual reading of amyloid-PET in MCI challenged: should we consider alternative methods?

Large scale production of 11C for PET-aided hadron therapy

Purification of medical 153Sm using radiation-resistant ionic liquids

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Introduction

Dear participants,

Welcome to the 6th edition of the Symposium on Medical Radioisotopes.

The very first edition of the symposium was organised in 2007 by SCK•CEN in Mol, Belgium. Since, very successful editions were organised at SCK•CEN, at the Royal Military Academy and at the Palace of the Academies.

The organisation of the symposium is an initiative by the European Isotope Transport Association (EITA), Isotopes Services International (ISI) and the Belgian Nuclear Research Centre SCK•CEN. It brings together international researchers, suppliers, service providers and users who take an active interest in the benefits of radioisotopes for healthcare.

This 6th edition strives to:  Promote the exchange of information about the perspectives of the world production of medical radioisotopes during the next decade;  Stimulate the discussion on challenges related to the distribution processes including safety, security, transparency and prompt delivery;  Present breakthroughs of research in radiopharmacy, medical imaging and nuclear medicine;  Describe new Belgian industrial and research initiatives.

The quality of the invited talks and posters by researchers in the field guarantees that this 6th edition of the Symposium will once again reflect the interest of all stakeholders for a sustainable and timely access to radioisotopes for research, diagnosis and therapy.

On behalf of the Organising and Scientific Committee, I thank all authors, chairs and participants for their valuable contributions and presence. Also, very sincere thanks to our generous sponsors for supporting the organisation of this symposium.

Prof. em. Frank Deconinck Chair of the Organising Committee

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Programme

08:15 – 09:00 Registration and welcome coffee

09:15 – 09:30 Opening Formal opening | Frank Deconinck, Conference Chair Introductory address | Bart Somers, Mayor of Mechelen

09:30 – 10:30 Session 1: Radioisotope production | Chair: Jean-Michel Vanderhofstadt 1: The new BR2 reactor - perspectives for radioisotope production | Bernard Ponsard (SCK•CEN and AIPES) 2: The MYRRHA accelerator - perspectives for radioisotope production | Lucia Popescu (SCK•CEN) 3: World status on reactor and cyclotron radioisotope production | Richard Zimmermann (MEDraysintell)

10:30 – 11:00 Coffee break and poster session

11:00 – 12:00 Session 2: Radioisotope Transport and Good Distribution Practice | Chair: Yvan Bruynseraede

4: Good Distribution Practice: challenges and implementation | Rob Dekkers (GE Healthcare and AIPES) 5: Security issues during transport and delivery | Yvan De Mesmaeker (ECSA) 6: Urban mobility and Good Distribution Practice | Milena Janjevic (ULB)

12:00 – 12:30 Special highlight by the Federal Agency for Nuclear Control | Chair: Michel Giot

7: Safety and security: general vision by FANC | Rony Dresselaers, Director Security & Transport (FANC) 8: The upcoming transport regulations | Rony Dresselaers, Director Security & Transport (FANC)

12:30 – 14:00 Lunch and poster session

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14:00 – 15:00 Session 3: Radiopharmaceuticals | Chair: Filip De Vos 9: Central vs. distributed radiopharmacies | Vicky Caveliers (UZBrussel, VUB) 10: The Ge/Ga generator: first evaluation | Philippe van Put (IRE-ELiT) 11: Safety/security issues in the hospital | Myriam Monsieurs (UGent)

15:00 – 16:00 Session 4: Medical Radioisotope Applications | Chair: Serge Goldman 12: Theranostics | Patrick Flamen (Bordet Institute) 13: Which radionuclide for solid tumour treatment? | Stéphane Lucas (UNamur) 14: Degenerative neurological diseases | Rik Vandenberghe (KU Leuven)

16:00 – 16:15 Poster prize ceremony Serge Goossens | CEO ISI & President EITA

16:15 – 16:30 Conclusions and closure Kristoff Muylle | President EANM

16:30 – 17:00 Reception

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Frank Deconinck Professor Emeritus Conference Chair

Frank Deconinck obtained his PhD in Medical Physics from the Vrije Universiteit Brussel (VUB). He was research associate at the University of California (UCSF) and research collaborator at Brookhaven National Laboratory. He is professor emeritus of medical physics at VUB. In the nuclear field, he is honorary chairman of the board of governors of the Belgian Nuclear Research Centre (SCK•CEN), vice-president of Belgonucléaire NV, member of the French Commission Nationale d'Evaluation (CNE), president of the Belgian Hadron Therapy Centre foundation and honorary president of the European Nuclear Society. He coordinates Rad4Med.be, the Belgian network for radiation applications in healthcare. In the socio-cultural field he organised, together with Mrs. Deconinck-De Ries, the exhibition “Tactile Graphic Art”, selected by UNESCO for the U.N. World decade for cultural development. Exhibitions were held in Belgium, Paris (UNESCO), Köln, Taejou, Osaka, Tokyo,...; he co-organised the International Very Special Arts Festival in Brussels, 1994. He is author, co-author or editor of 6 books, ± 100 articles, ± 200 communications and ± 200 invited talks, mainly on medical imaging. He received the Hewlett Packard prize for medical informatics in 1984 and the Familie Bruers-Colbert and daughter prize for his work on X-ray fluorescence in 1987.

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Bart Somers Mayor of Mechelen

Bart Somers is a Flemish politician, member of the Open-VLD party, where he has fulfilled various functions. He has been minister-president of the region of Flanders, party president for five years. Currently he is the Group chairman for Open VLD in the Flemish Parliament and Vice-president of the ALDE- group in the Committee of the Regions. He has been Mayor of the Belgian town of Mechelen since 2001 and a Member of the Committee of the Regions (CoR) since 2004. Bart was rapporteur for the opinion “Combatting radicalization: mechanism for prevention on a local and regional level” which was accepted on 15th of June in the Committee of the Regions.

Personal  Born in Mechelen on 12 May 1964

Study  Master in Law, KU Leuven

Professional activities  1992 – 1995: adjunct-chief editor VLD-citizen newspaper  1995 – 1997: VLD-spokesman (ad interim)  1995 – 1997: University employee VLD-senate group  1997 – 1999: VLD-spokesman  2004 – 2009: Open Vld-party chairman  2014 – …. : Group chairman Open Vld in the Flemish Parliament  2014 – … : Vice-president of the ALDE-group in the Comité of the Regions & CIVEX coordinator

Politcal activities  1994 – 2000: councillor Mechelen  1999 – 2004: federal MP  2001 – …. : Mayor of Mechelen  2004 – 2007: Flemish MP  2007 – 2014: federal MP  2014 – …. : Flemish MP

Government function  2003 – 2004: Prime minister of the Flemish government

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Jean-Michel Vanderhofstadt General Manager of IRE and IRE Elit President of AIPES Session Chair

Jean-Michel Vanderhofstadt is graduated from the Universities of Liège and Brussels, Belgium, where he obtained his degree of industrial pharmacist and post-degree in Business Management, respectively. From 1986 to 2004, he worked for SCA Mölnlycke in Belgium, Ireland, Czech Republic and Sweden as a quality control manager, product developer, production manager, site manager, general manager of the Czech subsidiary and R&D surgical business director, Gothenburg, Sweden. In 2005, he took the position of General Manager of a large Belgian company active in the food sector. Since June 2008, he is the General Manager of IRE, Fleurus, Belgium. He is also President of the company Transrad specialized in transportation of nuclear material, and represents IRE as director of Stérigénics and Oncidium.

He is appointed lecturer at the Universities of Liège, Brussels and Louvain-la-Neuve in Belgium, being in charge of a course on Business management.

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Bernard Ponsard Radioisotopes Project Manager, SCK•CEN – BR2 Reactor

Bernard Ponsard (Master in Physics, Université Catholique de Louvain, UCL, Belgium, 1983; Master of Science "Nuclear Energy", Université Catholique de Louvain, UCL, Belgium, 1985) joined the 'Belgian Nuclear Research Centre' (SCK•CEN) in Mol in 1985 as reactor physicist at the BR2 High-Flux Material Testing Reactor. In charge of the neutronic calculations of the BR2 reactor core and the interpretation of the related nuclear measurements for 30 years, he developed actively BR2's commercial productions of radioisotopes and NTD-silicon.

He is currently Head of Unit RSP, Radioisotopes and Silicon Production, at the BR2 reactor and in charge of the strategic development of new medical radioisotopes for nuclear medicine and of new products for the semiconductor industry within SCK's Institute for Nuclear Materials Science (NMS).

Since 2010, he is Chairman of the "AIPES Reactors & Isotopes Working Group", strongly involved in securing global supply of medical radioisotopes as Mo-99/Tc-99m, and Chairman of the "European Observatory Working Group for the European Supply of Medical Radioisotopes - Global Reactor Scheduling and Mo-99 Supply Monitoring".

Abstract The new BR2 Reactor - Perspectives for Radioisotope Production

The BR2 high-flux reactor operated by the Belgian Nuclear Research Centre (SCK•CEN) is not only one of the world's most powerful material testing reactors, it is also recognized as a major facility for the global production of radioisotopes. The refurbishment performed recently (February 2015 – June 2016) will ensure a safe and reliable reactor operation for another period of at least 10 years. The current operating regime based on 6 cycles (140 operating days) per year could be upgraded up to 8 cycles (200 operating days) subject to the economics. The availability of high neutron fluxes up to 1015 n/cm².s, large irradiation volumes and flexible irradiation conditions allow the production of high specific activity radioisotopes for NDT applications (Ir-192, Se-75, …) and nuclear medicine (Mo- 99/Tc-99m, I-131, Xe-133, W-188/Re-188, Ir-192, Sr-89, Lu-177, Sm-153, Re-186, Y-90, Er-169, Sn- 117m, P-32, …).

With 7.800 '6-day' Ci per week – the largest world's installed irradiation capacity for Mo-99 production – the BR2 reactor is able to meet 25% of the global Mo-99 demand in average and as much as 65% in peak periods. This crucial contribution could even be increased up to 100% in future to help securing the supply of Tc-99m which is used in 80% of the 30 million SPECT imaging procedures carried out worldwide annually.

In addition to the current production of radioisotopes for therapy (I-131, Lu-177, Ir-192, Ho-166, Y- 90, P-32, …) and for palliation of metastatic bone pain (Sm-153, Re-186, Re-188, Sr-89, Sn-117m, Ra- 223, …), nuclear medicine is offering new perspectives. Radioisotopes as Lu-177 are already largely

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used for targeted radionuclide therapy (TRNT) but others as Sc-47, Cu-67 and Tb-161 are under evaluation as they are medium-energy β- emitters similar to Lu-177 but with the advantage of having diagnostic partners. The concept of personalized medicine based on 'theranostics' is increasingly seen as a promising approach in which single radioisotopes or 'matched pairs' (Sc-44/Sc-47, Cu- 64/Cu-67, Tb-152/Tb-161, Tb-155/Tb-161, …) are selected to enable pre-therapy imaging and dosimetry followed by the administration of an appropriate therapeutic dose to minimize the effect on healthy tissues. Other procedures using Y-90 and Ho-166 microspheres benefit of increased interest for the treatment of metastatic liver cancer. Last but not least, the production of α-particle emitters from the irradiation of Ra-226 are investigated for targeted alpha therapy (TAT).

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Lucia Popescu Head of the Proton Target Research Unit, SCK•CEN

Dr. Lucia Popescu obtained a PhD in nuclear physics at Ghent University in 2005. In the period 2001-2007, she conducted nuclear physics studies at hadron–accelerator facilities in The Netherlands, Japan and South Africa. Lucia joined SCK•CEN in October 2007, starting an experimental campaign for neutron induced fission measurements at the BR1 reactor. Since 2010, she is the coordinator of the SCK•CEN activities within the Belgian research initiative on eXotic nuclei (BriX) network, being involved in experimental studies at Isotope Separation On-Line (ISOL) facilities. In 2010 she became leader of the ISOL@MYRRHA project and built a research group performing physics experiments and R&D for advanced ISOL target technology. In 2010 she became the head of the Physics and Technology Innovation unit, which later evolved into the Proton Target Research unit within the Accelerator Project group of the Advanced Nuclear Systems institute at SCK•CEN. The activities of her group are focused on production of (innovative) isotopes for physics and medical applications. Since 2011, Lucia is representing the SCK•CEN in the national accompanying committee "European sources for synchrotron radiation and neutrons" (NAC-SRN). She is the co-founder and coordinator of the Belgian Eurisol Consortium (BEC) and in 2014 became the Belgium representative in the EURISOL steering committee.

Abstract The MYRRHA accelerator - Perspectives for Radioisotope Production

One of the important applications within the MYRRHA project at SCK•CEN is the production of medical isotopes by using protons from the linear accelerator. Given the high-energy and high- intensity of its proton beam, MYRRHA allows production of a variety of isotopes in large quantities. Next to already established accelerator isotopes, a large-range of innovative isotopes will become therefore available for pre-clinical and clinical studies eventually evolving into systematic production. The phased-implementation of the MYRRHA project makes possible to have an operational Proton Target Facility on site already in 2025, at the 100-MeV beam line of the linear accelerator. The presentation will introduce the project and its planned facility discussing the perspectives for radioisotopes production.

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Richard Zimmerman President, MEDraysintell

Richard Zimmermann is a chemistry engineer and PhD in Organic Chemistry (Strasbourg, F) with a post-doc at Georgetown University, Washington DC, who spent almost 15 years working with the conventional pharmaceutical industry in the research departments of Beecham (F - cardiology) and Solvay Pharma (F, D, NL - immunology then gastroenterology) before joining as Director of R&D the Radiopharmaceutical Industry with CIS bio international (Saclay, F), later a subsidiary of Schering Pharma. For three years he was also in charge of building the European PET manufacturing centers for CIS/IBA and in 2006 he took over the position of VP Business Development for IBA Molecular. During this period, he has been leading the AIPES PET working group for 3 years and very recently he founded Oncidium, a foundation supporting the development of radiotherapeutics. In 2012, he created his own consulting company, Chrysalium Consulting, specialized in the support and industrialization of radiopharmaceuticals. He is President of the companies Medisystem and ANMI respectively since 2013 and 2015. So far he did spend 17 years in the Nuclear Medicine environment and he published several review articles as well as a general audience book on that topic translated in French, English and Spanish. His main interest is now focusing on the long term evolution of nuclear medicine through the identification and evaluation of industrial, regulatory and economic constraints with expert reports published through the partnership MEDraysintell.

Abstract World status on reactor an cyclotron radioisotope production

Over the past 70 years the needs for medical radionuclides have considerably evolved in a way that led to a selection of the most appropriate elements for the present and next 10 years applications. In parallel the tools (reactors, linear accelerators, cyclotrons, but also generators) have also been or are in progress to be adapted to this demand and the priorities of today have considerably changed compared to 10 years ago. As the investment in such production tools remains the initial highest budget from the entire drug manufacturing process, it makes sense also to have a better knowledge about the radionuclides that will have the highest chances to be used in nuclear medicine during the next 20 to 25 years and the life time of these tools. Therefore it is also important to know which specific equipment at which location can answer to these needs. Type of production tool and location of this tool will directly impact the cost of the radionuclide at the level of the end user. The presentation will focus on the selection of radionuclides of interest for the near future and describe the installed base and capacity of production for all these tools all over the world that will be available for this purpose. Criteria for selecting the next generation (post 2025) of radionuclides among the ones that are nowadays considered as ‘exotic’ will also be discussed in order to show which ones could become alternatives or improvement of today’s best choices.

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Yvan Bruynseraede Professor Emeritus, KU Leuven Session Chair

Yvan Bruynseraede is Professor Emeritus at the University of Leuven (KU Leuven). After receiving his PhD (1967) in physics from the KU Leuven, he was a research fellow and research associate at CERN, Geneva. In 1971 he moved back to Leuven to build-up a new laboratory. He was until 2003 Head of the Laboratory of Solid-State Physics and Magnetism, KU Leuven. His research is in the domain of solid state physics, particularly the properties of mesoscopic and nanoscopic structures. In the nuclear field, he was a member of the board of governors of the Belgian Nuclear Research Centre (SCK•CEN), and chairman of the Scientific Advisory Committee. He is Past-President of the Royal Belgian Academy, member of the Royal Society in Göteborg, the European Academy in Vienna, and is a Fellow of the American Physical Society. He was/is chairman or member of National and International Advisory and Reviewing Committees, Research Foundations and Councils. His work has been internationally recognized and resulted in more than 450 publications, numerous invited talks, and active collaboration with scientists all over the world. He is together with Ivan Schuller (UCSD) the recipient of the prestigious 2007 IUMRS SOMIYA Award, which recognizes outstanding research conducted by teams from at least two continents. In 2016 he was Chairman of the Forum on Outreach & Engaging the Public (FOEP) of the American Physical Society.

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Rob Dekkers Global Logistics Manager SPECT/PET and Dangerous Goods Compliance, GE Healthcare and AIPES

Rob Dekkers’ current role is Global Logistics Manager SPECT/PET and Dangerous Goods Compliance Working for GE Healthcare, Core Imaging, located at Eindhoven, NL In his role he is responsible for the global distribution and compliance of the GE Healthcare radiopharmaceuticals. He is the Chairman of the AIPES Transport Working Group Rob graduated from the Eindhoven University of Technology; He received his Master of Science degree in 1988 from the faculty “Technology and Society”.

He is a trained Level 3/C radiation protection professional He has many years of experience with the transport of dangerous goods by road (ADR) and air (IATA) and is IATA certified for the Transport of Radioactive Material (Class 7) by Air. He has been a certified ADR Dangerous Goods Transport Safety Adviser. He has worked in several roles in the radiopharmaceutical business. This includes customer service, warehousing and distribution and managing the implementation of validated ERP systems to support the radio-pharmaceutical business. Over the past few years he has an increased focus on the implementation of the new GDP guidelines.

Rob was a speaker at the: Global Pharmaceutical Distribution Summit, taking place in Amsterdam from the 23-25 September. 2103 "5th Symposium on Medical Radioisotopes 2015-2020: Production and transportation challenges" in Mol, Belgium. On May 5th 2015 5th ANNUAL LIFE SCIENCE COLD CHAIN & TEMPERATURE CONTROLLED LOGISTICS in Brussels, Belgium during the period of 12th - 13th MAY 2015. 15th Annual Cold Chain, temperature controlled logistics EUROPE In Frankfurt, 26-27th Jan 2016

Abstract Good Distribution Practice: challenges and implementation

This presentation cover the constraints and challenges of moving radiopharmaceuticals, from the raw material to the end customer, the patient. Most radiopharmaceuticals tend to be short half-life nuclides used to diagnose or treat disease. This presentation will focus on the nuclide Iodine-123 Iodine-123 is a nuclide used in diagnostic agents for diagnosing Parkinson’s disease, the detection of tumors, establishing heart failure and other diseases.

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Many millions of scans across the globe are performed in a nuclear medicine department by administering a radiopharmaceutical to the patient. The supply and manufacturing chain for Iodine-123 products, from cyclotron to end-customer, (including the chemical process to produce sterile material) must be well choreographed. Iodine-123 has a half-life of 13.2 hours, the process of making the raw material using a cyclotron, processing and transporting must happen on the same day. Any delay invariably means that the product will not be able to be used. To add to the challenges of the product being radioactive and therefor meeting the requirements of the Dangerous goods regulations, it also must meet the strict requirements of intravenously injectable drugs (GMP), followed by the guidelines for Good Distribution practices (GDP). Because of the special nature of radiopharmaceuticals and the sometimes conflicting setups for dangerous goods and pharmaceuticals, fully complying with GDP is a challenge On top of that there is an increased focus on airfreight security which could potentially delay the shipments of these products.

Delays have an impact on the Healthcare system, not just monetary for the manufacturer but also the cost to Healthcare system for re-scheduling, loss of scanner time and of course the discomfort to the patient.

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Yvan De Mesmaeker Secretary General, ECSA

Yvan De Mesmaeker is a Civil Engineer with over 25 years of professional experience in Corporate Security and Emergency Response. The European Corporate Security Association - ECSA, is a non for profit Professional Association of Managers and Officials in charge of the Security & Resilience of Corporations and International Institutions. -> https://be.linkedin.com/in/yvandemesmaeker

In addition ir. Yvan De Mesmaeker is:

 Managing Director & Senior Security Advisor at Omega Risk, an independent advisory practice that assists Corporations, Organisations and Institutions in the fields of Security, Emergency Response & related Strategic Issues  Vice Chairman of the Board of the Security Office of the Antwerp World Diamond Centre (AWDC)  Director of the High Studies Police, Justice & Corporate Security, organized by ECSA, the College for Senior Police Officers, the Judicial Training Institute, the Universities of Gent and Liège and the Federation of Enterprises in Belgium  Secretary General & Executive Committee Member of ATHENA, the Alumni Association of the Graduates from the High Studies Security & Defence, organized by the Royal High Institute for Defence (RHID) and the Royal Institute for International Relations (Egmont)  Secretary of the US Department of State Overseas Security Advisory Council, Belgium Brussels Chapter

Abstract Security issues during transport and delivery

This lecture will focus on fundamental concepts and ideas when setting up the security of operations in the nuclear industry. It will examine the difference between box ticking compliance and effective security and suggest a different way of looking at the mandatory nuclear security framework.

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Milena Janjevic Senior Researcher and Lecturer, ULB

Dr. Milena Janjevic (F), a Polytechnical Engineer, holds a a Ph.D in Transport and Logistics Engineering and is a Senior Researcher and Lecturer at Université Libre de Bruxelles. She is an invited Lecturer at Ecole des Mines (Paris), a visiting scholar at the MIT Megacity Logistics Lab (Boston) and at the the Center of Excellence for Sustainable Urban Freight Systems at Rensselaer Polytechnic Institute (New-York). Her field of research and expertise which has been proven in a large number of local, regional, European and international projects include supply chain optimisation, intermodal transport/logistics and urban freight logistics with a particular focus on the modeling of innovative concepts/strategies and the use of new technologies

Abstract Urban mobility and Good Distribution Practice

The supply chain of medical radioisotopes needs to follow strict time and security constraints and involves specific transportation conditions. The last part of the transportation chain often takes place in highly congested urban areas, resulting in potential challenges with regards to the efficiency and the reliability of the delivery. City logistics research field studies distribution models currently employed by companies in urban environments. This presentation aims in presenting some of the main challenges, trends and best practices in the field of urban goods distribution in order to identify potential contribution to management of the supply chain for the medical radioisotopes.

First of all, the presentations addresses the specific conditions under which urban deliveries need to be operated and we discuss the consequences on their performance. Secondly, it demonstrates some innovative urban logistics solutions that are currently employed in the cities. The presentation then highlights the specific constraints of the transportation of the medical radioisotopes in urban areas and identifies the performance dimensions of this type of supply chain. It confronts those performance dimensions with those typically employed in urban logistics and concluded with regards to the potential contribution of the urban logistics research field to the optimization of the medical radioisotopes supply chain.

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Michel Giot Professor Emeritus, UCL Session Chair

Michel Giot is Emeritus Professor of the Catholic University of Louvain (UCL, Louvain-la-Neuve, Belgium), where he got his doctoral degree in mechanical engineering in 1970. During his career he was active in research in two-phase flows and heat transfers, teaching thermodynamics, transport phenomena, nuclear thermal-hydraulics and major technological hazards. He was Dean of Engineering of UCL from 1989 to 1994, and chair of the Board of the Ecole Nationale Supérieure d’Ingénieurs de Constructions Aéronautiques (ENSICA – Toulouse) from 2001 to 2006. He contributed to the creation of the Belgian Nuclear Higher Education Network (BNEN) , an inter-university postgraduate nuclear engineering programme, and to the creation of the ENEN network. He is currently Member of the Board of SCK•CEN (the Belgian Nuclear Research Centre) and of Isotopes Services International n.v./s.a. (ISI), a radio-isotopes transportation company. He is Honorary Chair of the Scientific Council of SCK•CEN and Member of several scientific advisory boards including the scientific council of ionizing radiations (AFCN-FANC), the scientific committee of the nuclear energy division of CEA (France) and the Comité de Visite of IRSN (France). In the recent times he was invited by the French AERES and HCERES to chair several scientific evaluation committees. Active in international editorial boards and in the organisation of conferences and symposia, Michel GIOT was lead guest editor of the special issue of “Science and Technology of Nuclear Installations” devoted to TOPSAFE 2008, and of the special issue of “Progress in Nuclear Energy” devoted to EUROSAFE 2013. He has chaired the scientific committee of the ANIMMA (Advancements in Nuclear Instrumentation, Measurement Methods and their Applications) Conferences from 2009 to 2017. Member of the European Academy of Sciences and Arts and Doctor h.c. of the University Politehnica of Bucharest, he received several Belgian and French distinctions. He authored or co-authored several books or parts of books, about two-hundred papers in journals or at conferences, and one patent. Areas of expertise Thermodynamics, Fluid Mechanics, Heat Transfer, Multiphase flows, Nuclear Reactor Safety, Major Technological Hazards Scientific evaluation processes January 2017.

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Rony Dresselaers Director Security and Transport, FANC

Rony Dresselaers was awarded a Master’s degree in industrial sciences, nuclear technology and radiochemistry from XIOS Hasselt in 1987. He is also holder of a post graduate in operations management of the University of Leuven. From 1989 to 2007 he worked for FBFC International, a subsidiary of Areva producing UO2 and Mox fuel assemblies for nuclear reactors. At FBFC he held various positions in process engineering, project management and operations management. In his last position at FBFC International he was the manager for the uranium productions and member of the direction of the facility. In 2008 he joined the Federal Agency for Nuclear Control as Director for the department of Nuclear Security and Transport. Within the FANC, the Security & Transport department is organised in 2 services. The nuclear security service is in charge of the nuclear security and the physical protection of radioactive materials including nuclear materials. The service has also responsibilities in the frame of safeguards and nuclear non - proliferation by ensuring the interface between the operators and the IAEA and Euratom inspectorates. The Import and Transport service is in charge of issuing the import and transport licences, package approvals certificates, ADR training and regulations. At international level he is member of the International Steering Committee on denials of shipment and he is also nominated as a member of the Nuclear Security Guidance Committee both at the IAEA. He is also an active member of the European Association for the Competent Authorities for the transport of radioactive materials. In 2014 he was the chairman for the European Nuclear Security Regulators Association.

Abstract Safety and security: general vision by FANC & The upcoming transport regulations Revision of the Belgian Legislation for the Transport of Radioactive Material

Rony DRESSELAERS, Martine LIEBENS, Guy LOURTIE

Currently, the transport of radioactive material in Belgium is governed by chapter VII of the GRR (Royal Decree of 20 July 2001 laying down the General Regulation for the Protection of the Public, Workers and the Environment against the Hazards of Ionising Radiation). This current license-based system, dating from 1963, has contributed to the safe and secure record that we have achieved in Belgium so far but we are convinced that a simplification of the current system is necessary.

The main goal of the revision of the Belgian legislation for the transport of radioactive material is to evolve from a license-based system combining reporting and notification with inspections toward a

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new system mainly based on registration, with only a limited number of licenses being required after registration. This new system will focus on inspections and compliance audits in order to ensure compliance with the national and international regulations for the safe transport of radioactive material. It should reduce the administrative burden for the FANC (Federal Agency for Nuclear Control) and its stakeholders involved in the transport of radioactive material on the Belgian territory (designers and manufacturers of packages, organizations in charge of the maintenance and repair of packaging, consignors, carriers, consignees).

On the other hand, it is of crucial importance that this change in our way of working does not affect the safe, secure and sustainable transport of all radioactive material throughout our territory. Furthermore, this new legislation should not impact our knowledge of who is carrying what, when and in which conditions within the Belgian borders.

The project was started up in January 2013 not only to draft the new legislation but also to prepare the implementation and the organization of the Import & Transport Section within the FANC, the Belgian regulatory body.

The paper will discuss the most important aspects considered in this challenging project as well as the consultation process with the sector during the concept development stage, and will present the new Belgian legislation for the transport of radioactive material and the new organisation of the FANC’s Import & Transport Section.

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Vicky Caveliers Head of Radiopharmacy Unit, UZ Brussel Professor, Faculty of Medicine and Pharmacy, VUB

I obtained my PhD Degree in Pharmaceutical Sciences in 2003 at the Vrije Universiteit Brussel (VUB) and I am since appointed Head of the Radiopharmacy Unit at the University Hospital UZ Brussel. I am a certified Radiopharmacist and 10% ZAP Professor at the In vivo Cellular and Molecular Imaging Laboratory (ICMI) in the Faculty of Medicine and Pharmacy of the VUB. In the clinic I am responsible for the preparation, quality control, quality assurance and release of radiopharmaceuticals for patient administration. Recently I became the coordinator of the Brussels Imaging Pharmacy (BIP) project, a centralized PET radiopharmacy in compliance with Good Manufacturing Practices (GMP), together with the hospitals Bordet and Erasme. The research focus of the ICMI laboratory is on the development of new radiopharmaceuticals based on camelid single domain antibody fragments (also called VHH or Nanobodies) for diagnosis and radionuclide therapy applications. These activities include optimization of (automated) radiolabeling procedures, purification methods and formulation of the radiolabeled probes, followed by in vitro and in vivo evaluation in terms of biodistribution, in vivo stability and targeting potential. The main goal of our research is translation of these preclinically validated radiopharmaceuticals to early phase clinical trials, including fulfilling all regulatory requirements In 2012, a first-in-human clinical trial was initiated with an in-house developed 68Ga-labeled anti- HER2 VHH for PET imaging in breast cancer patients. I supervise master and PhD students working on the above mentioned topics and I am (co)-author of 75 publications in scientific journals with an international referee system.

Abstract Central vs. distributed radiopharmacies

Because of the intrinsic nature of radiopharmaceuticals with their short half lives and thus limited shelf-life, they are ideally prepared in the proximity of the nuclear medicine patient. For this reason, nuclear medicine facilities in the majority of the European countries have their own radiopharmacy within or nearby the nuclear medicine department, primarily for the preparation of 99mTc- radiopharmaceuticals from commercialized generators and kits. Alternatively, in other countries such as in the US and UK, conventional radiopharmacy practice has emerged to centralized radiopharmacy production sites from where individual patient doses or multidose units are distributed to several hospital nuclear medicine departments. Historic reasons for this development were either commercial interest or, as a result of strict regulatory requirements demanding high costs for infrastructure and specialized staff. Both scenarios have to deal with their own advantages and limitations.

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The case of PET radiopharmaceutical production is more complex. On the one hand the use of very short living isotopes requires the production to take place nearby an on-site cyclotron or generator. Additionally, in-house production allows for clinical research and development of new radiopharmaceuticals. On the other hand, the investment costs in highly sophisticated equipment and dedicated staff are high and operational costs are rising substantially due to the implementation of Good Manufacturing Practice (GMP) standards imposed by the regulatory agencies, even in a small-scale hospital setting.

In order to cope with these constraints, 3 academic Brussels hospitals (UZ Brussel, Institut Jules Bordet and Hopital Erasme) decided to cluster their radiopharmacy activities within the Brussels Imaging Pharmacy (BIP), a centralized GMP production site for PET radiopharmaceuticals.

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Philippe van Put Business Development Department Manager, IRE-ELiT

Academic background  Master in Nuclear Sciences Engineering (speciality: radiation detection and measurement) in 1991 from I.S.I.B – Brussels (graduation lecture in nuclear medicine imaging)  Master in Radiation Protection and Applications of ionizing radiations in 1999 from U.C.L - Louvain-la-Neuve (graduation lecture on radiological waste characterisation by gamma spectrometry)  Master in Management in 2007 from ICHEC-Entreprises - Brussels

Professional activities  From 1993 – 1997: system and application engineer at CANBERRA BENELUX  From 1997 – 2000: service manager at CANBERRA BENELUX  From 2000- 2007: head of nuclear metrology department at Institut des Radioéléments  From 2007 – 2009: business development manager Europe for Nuclear Power Plant instruments at AREVA – Nuclear Instrumentation Business Unit  From 2009 – 2010: director of health physics product development at AREVA – Nuclear Instrumentation Business Unit  From 2010 – now: business development manager for radiochemical and radiopharmaceutical at IRE – IRE ELiT

Miscellaneous  Secretary of the Belgian Nuclear Society from 2004 to 2005

Abstract The Ge/Ga generator: first evaluation

The Ga68 generator appears to be on of the product the most cited in recent publications and communications. Such excitement about a radioisotope has not been seen since years when F18 became available to PET centres. The possibilities for using such a generator in routine practices rely on the ability of the industry to make this product as simple to use as a Tc99m generator used in daily SPECT practices. This paper will address the emerging progresses that will make such statement a reality.

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Myriam Monsieurs Head, Department of Health Physics, UGent

Myriam Monsieurs was born in Tongeren on February 5th 1971. She holds degrees for bachelor in chemistry and master in biotechnology. As she realized that a life stuck in the lab was not for her, she went on to the Ma-na-Ma studies of biomedical engineering techniques in hospital radiation physics. In 1996, her thesis in nuclear medicine focused on “radiation protection guidelines for 131-I therapy for thyroid disease”. This study culminated first in a multicenter trial (1997-1998: ADAC advanced clinical research grant) and in 2003 in a medical PhD “Patient dosimetry and radiation protection issues for radionuclide therapy using 131I”. The scientific relevance is highlighted by winning of the following awards: Mallinckrodt Benelux award 1997, Alavi Mandell award (Journal of Nuclear Medicine) in 2000 and the Mutagenesis poster award in 2001. Myriam works at Ghent University (UGent) as health physicist class II since 2001 and became head of department in 2015. As such she was involved in the unloading and decommissioning of the nuclear research reactor Thetis, the removal of unused radioactive sources and the preparations for the dismantling of the accelerator park of UGent.

Abstract Safety and security in a hospital environment

Radiation safety has always been a key object in the hospital environment. Radiation therapy, was of concern because of the high dose rates and in nuclear medicine due to the use of open sources the risk for contamination is also present. Therefore, over the last 40 years, the sector has developed a multitude of tools, safety systems, procedures and training/education to deal with these risks. During the last 15 years, additional radioisotopes have been introduced into the hospital. The use of the positron emitters 18-F, 11-C and especially 68-Ge/Ga for PET imaging, have prompted the need for automation. The introduction of alpha emitters such as 223-Ra for therapy prompts a strict follow-up to prevent internal contamination. Traditionally, security has always played a less important role in the hospital. This is mainly due to the international organizations putting their emphases on nuclear installations and HASS (high activity sealed sources). Although the source term in the hospital is much smaller in comparison, medical facilities are much more common than nuclear installations. Sources within the hospital tend to be very diverse (source, patient, waste, …) and are usually mobile. Transport of radioactive sources happens on an almost daily bases and hospitals also tend to be very open facilities.

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If left unshielded, medical sources are certainly capable of inflicting serious harm on innocent bystanders. Unsealed nuclear medicine sources can cause internal contamination in case of uncontrolled spread. Hospitals therefore do present a valid security concern. It is certainly worthwhile to assess the current security status in your hospital. It will provide a good starting point for improvement, one “bite size” at a time. For a security culture in the hospital to have any effect, it should be linked to the existing safety culture. In fact, most existing safety procedures will also enhance security. It might just be as easy as preventing access through certain doors, keeping track of sources and actually following the existing procedures. Other procedures could be further extended. Examples are the REX procedure (return on experience) that could be extended upon to (internally) report minor incidents involving security issues. Another would be to enhance security of information, both digital as well as on paper, to the same level as patient data security. However, any safety/security system is only as good as the people practicing it. People should be motivated to follow the rules by making them aware of the existing threats and of their specific role in the chain of events. The topic of personnel security and “trustworthyness” cannot be ignored, but it is still foreign to the hospital environment. The FANC (Federal Agency for Nuclear Control) needs to issue guidelines on how this should be implemented and how far it should extend.

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Serge Goldman Director and Director of the Laboratoire de Cartographie du Cerveau, ULB - Erasme Hospital Session Chair

Serge Goldman is MD with successive certifications in neurology and in nuclear medicine and a thesis leading to the “agrégation de l’enseignement supérieur” in Medical Science. He is head of the Department of Nuclear Medicine and the PET/Biomedical Cyclotron Unit at ULB - Erasme Hospital since 2002. He is Director of the Laboratoire de Cartographie du Cerveau at ULB - Erasme Hospital. He has published 264 peer-reviewed articles during the last 30 years (H-index: 48; 6969 citations; from Scopus). Most of this scientific production relates to PET imaging, including for animal models. His main field of research is imaging of brain tumors with a particular stress put on the integration of molecular imaging in therapy targeting. Other fields of interest are imaging for cell tracking and neurological applications of PET, in particular in the domains of neurodegeneration, epilepsy and development. He has been President of the Belgian Society of Nuclear Medicine from 2007 to 2010.

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Patrick Flamen Professor and Head of the Nuclear Medicine Imaging and RadionuclideTherapy department, Jules Bordet Institute, ULB

Patrick Flamen, MD, PhD, is since 2003 the head of the Nuclear Medicine Imaging and RadionuclideTherapy department of the Jules Bordet Institute, a dedicated comprehensive university cancer institute located in the heart of Brussels, and part of the Université Libre de Bruxelles (ULB). In 2016 his department performed more than 3500 SPECT-CT and 6000 PET-CT studies, and about 175 radiomolecular treatments. The available diagnostic systems include a PET-CT, a SPECT-CT, and a dual head SPECT camera. Patrick Flamen graduated at the Medical School of the University of Ghent, Belgium, in 1990. He specialised in Nuclear Medicine at the Vrije Universiteit van Brussel (VUB) in Brussels, Belgium. Thereafter, he worked for 5 years in the University Hospital of Leuven, Belgium, where he obtained a PhD degree in Biomedical Sciences in May 2001 on the use of FDG PET in Digestive Oncology. He presently has an academic appointment at the Université Libre de Bruxelles (ULB). His research activities mainly focus on the use of positron emission tomography (PET-CT) for Molecular Imaging in clinical and translational research in oncology. He is involved in multiple academy and industry driven trials on the developement and validation of molecular imaging biomarkers for assessing and predicting cancer treatment efficacy and patient outcome. He is also the driving force of the development of new targeted radionuclide treatments (radioembolization of liver tumors using Y90-labeled microspheres; radioimmunotherapy of CD20-positive lymphoma with Y90-rituximab; Radium-223 for bone metastasis; Lutetium-177 octreotate for neuroendocrine tumors). He is the (co)author of 101 peer reviewed scientific articles and three book chapters.

Abstract Theranostics

Currently, personalized medicine has become the core paradigm in modern oncology. Nuclear Medicine offers the unique opportunity of personalized targeted radiotherapy based on the “theranostics concept”: a same radiotracer targeting a specific molecular biomarker of the tumor is used for both diagnosis (when labeled with an isotope for PET or SPECT imaging) and molecular radiotherapy (when labeled with a beta- or alpha emitting isotope). The use of theranostic radiopharmaceuticals allows pretherapeutic simulation of the molecular radiotherapy (including testing for target expression; pharmacokinetics analysis; predictive dosimetry) allowing personalized dosimetry and prediction of efficacy/toxicity. In Belgium, the Institut Jules Bordet has been one of the major protagonist in the development and clinical introduction of radiotheranostics such as Peptide Receptor RadioTherapy (PRRT) for

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neuroendocrine tumors, and RadioImmunoTherapy (RIT) in lymphoma. This lecture will provide an overview of most recent nuclear medicine developments in cancer theranostics in the following areas:  68Ga/177Lu-octreotide for neuroendocrine tumors  99mTc-MAA/90Y-microspheres for radioembolization of liver tumors  89Zr/90Y-rituximab for CD-20 positive lymphomas  99mTc-MDP/223Radium (alpha emitter) for therapy of bone metastasis  68Ga/177Lu-PSMA (under development) for therapy of prostate cancer

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Stéphane Lucas Professor in the physics department, UNamur Director of the LARN laboratory

Stéphane Lucas is professor in the physics department of the University of Namur. He is the director of the LARN laboratory. Its current research interest includes radioisotope production by particle accelerator for medical applications, cell response to particle irradiation, novel fabrication methods of radioactive medical devices, internal dosimetry and material processes by plasma discharges. He received its PhD in Material Science in 1991 from the University of Namur. After a post-doc in the university of Aarhus, Denmark, where he studied the mechanical properties of thin coatings by nano- indentation, he spent 5 years in the research centre of Arcelor-Mittal working on new technologies for on-line steel-coatings by plasma discharges. In 1996, he joined the company Ion Beam Application in Louvain-La-Neuve where he developed high current cyclotrons for radioisotope production. Before moving back to the University of Namur in 2003, he has been appointed general Manager of IBA-Radioisotope where he was in charge of the production of new radioactive medical devices for the treatment of cancer. Among his current teaching duties, one can cite Biophysics, Basis of nuclear medicine, production of radioisotopes (University of Namur, Belgium), internal dosimetry (ULB, Belgium). He holds a Master in Business and Administration and has more than 100 publications and 10 patents. The ongoing research extends nowadays from the material science to life science field: In vitro cell response to particle ionizing radiation (proton, alpha, lithium and carbon) is studied thanks to its particle accelerator, the original vacuum deposition methods are now used to produce radioactive nanoparticle for radioimmunotherapy (RX, gamma and beta emitters), and Monte Carlo simulation tools are used to study dose delivery to cancerous tumors loaded with nanoparticles- radiolabelled MAB.

Abstract Which radionuclide for solid tumour treatment?

Radioimmunotherapy uses radionuclides labelling of monoclonal antibodies (mAb’s) to deliver ionizing radiation to tumour cells. Efficacy and toxicity of the treatment are mainly influenced by the antibodies biokinetics and biodistribution, but also by radionuclides physical properties. Today, various -emitters coupled to mAbs are being tested and compared to eradicate tumour tissues. If this technique is well adapted to treat radiosensitive haematopoietic malignancies, clinical studies have always shown poor therapeutic effects on solid and radioresistant tumours. This lack of success might be partly explained by the fact that these solid tumours are less sensitive to ionizing radiation and require doses larger than 60 Gy to be sterilised. Today, numerous research studies are focused on optimizing radioimmunotherapy by increasing the absorbed doses through a better accumulation

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or a better penetration of radiolabelled antibodies. But doses still remain insufficient to trigger a good treatment response. Another solution to maximize the deposited doses inside the solid tumour would be to increase the number of radionuclides coupled to each antibody. Previous work from our group has shown that an increase in the number of 90Y labelled to each antibody could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I and 188Re are used. Tumour control probability (TCP) and Normal Tissue Complication Probability (NTCP) curves versus the number of radionuclides per mAb were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius, and for nano-objects (i.e., a radiolabelled antibody) distributed uniformly or non-uniformly throughout the tumours (e.g. Non-small-cell-lung cancer (NSCLC)). 90Y and 188Re are the best candidates for solid tumour treatment when the mAb is radiolabelled with only one radionuclide. Furthermore, no matter the radionuclide properties, high values of TCP are observed without toxicity if the number of radionuclides per nano-object increases.

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Rik Vandenberghe Professor of Neurology at the Faculty of Medicine, KU Leuven

Rik Vandenberghe received his medical training at the Faculty of Medicine, Katholieke Universiteit Leuven, Belgium (KU Leuven). He performed his PhD research from 1993-1997 at the Laboratory for Neuro- and Psychophysiology, KU Leuven (advisor Guy Orban) and at the Wellcome Department of Cognitive Neurology, Institute of Neurology, London (advisor: Cathy Price, Richard Frackowiak). He obtained his PhD degree in 1997 at the KU Leuven. In 1999-2000 he spent a Human Frontiers Science fellowship at the Cognitive Neurology and Alzheimer’s disease Center (CNADC, director Marsel Mesulam), Northwestern University, Chicago. Rik Vandenberghe is registered as a neurologist since 1999. Rik Vandenberghe is currently Professor of Neurology at the Faculty of Medicine, KU Leuven, since 2000 director of the memory clinic of the University Hospitals Leuven (http://www.uzleuven.be/geheugenkliniek/ ), and since 2005 head of the Laboratory for Cognitive Neurology (LCN), KU Leuven (http://med.kuleuven.be/lcn/). The memory clinic of the University Hospitals Leuven is part of the European Alzheimer's Disease Consortium (EADC) and provides early diagnosis, treatment and care for home dwelling patients with Alzheimer's disease (AD) and frontotemporal degeneration (FTD) across the disease spectrum with a special interest in early-onset dementia as well as atypical variants (primary progressive aphasia, posterior cortical atrophy). The Laboratory for Cognitive Neurology combines research in cognitively intact volunteers with studies in patients with cortical neurodegenerative disease and focal cortical stroke using different methodologies from behavioral assessment over functional magnetic resonance imaging and electrophysiology to molecular imaging. Rik Vandenberghe is former president of the Flemish Society for Neurology, member of the Society for Neuroscience, the Society for the Neurobiology of Language, the Organisation for Human Brain Mapping and the Alzheimer's Association International Society to Advance Alzheimer Research and Treatment (ISTAART), and founding member of the International Society for Frontotemporal Dementias. He is serving on the Research Council KU Leuven (2014-2018, board member 2016-2018). He has served on the scientific programme committee of Memorabel (Deltaplan Nederland, ZonMw) (2013- 2016) and on the scientific programming committee of the Alzheimer Association International Conference 2012-2015 (2014-2015 theme lead of the theme ‘diagnosis and prognosis), chaired the reviewing committee of the German Kompetenz Network for Dementia (2011-2013) (Bündesministerium for Forschung und Bildung) and served on the international reviewing panel for the Joint Programming initiative on Neurodegenerative Diseases (JPND) and the Innovative Medicines Initiative (IMI-1 and IMI-2). He is member of the editorial board of NeuroImage Clinical and of Frontiers in Human Neuroscience. He has received several prizes including the Inbev-Baillet Latour Prize for Clinical Research 2007 and the Queen Elisabeth Medical Foundation UCB award for Neuroscience Research 2008. His research is mainly funded by the Flemish Research Foundation (FWO), the KU Leuven, and the federal government (Interuniversity Attraction Pole programme). He has published more than 200 scientific papers in high-ranking peer-reviewed international journals such as Nature, Nature Neuroscience, the Journal of Neuroscience, Brain and Annals of Neurology (first- and last-author 6th Symposium on Medical Radioisotopes page 36 of 58 SCK•CEN/22527775 ISC: Public

papers) (Web of Science Sum of times cited 7713, average citations per article 44; h index Feb 1st 2017 41).

Five peer-reviewed key publications that are representative of scientific career: 1. Vandenberghe R, Van Laere K, Ivanoiu A, Salmon E, Bastin C, Triau E, Hasselbalch S, Law I, Andersen A, Korner A, Minthon L, Garraux G, Nelissen N, Bormans G, Buckley C, Owenius R, Thurfjell L, Farrar G, Brooks DJ. 18F-flutemetamol amyloid imaging in Alzheimer's disease and mild cognitive impairment: a phase 2 trial. Annals of Neurology 68, 319-329, 2010 (Web of Science times cited 268) 2. Nelissen N, Van Laere K, Thurfjell L, Owenius R, Vandenbulcke M, Koole M; Bormans G, Brooks DJ, Vandenberghe R. Phase 1 study of the Pittsburgh Compound B derivative 18F- flutemetamol in healthy volunteers and patients with probable Alzheimer disease. J Nucl Med 50, 1251-1259, 2009 (times cited 133) 3. Vandenberghe R, Price CJ, Wise R, Josephs O, Frackowiak RSJ. Functional anatomy of a common semantic system for words and pictures. Nature 383; 254-256, 1996 (times cited 815) 4. Cruts M, Gijselinck I, van der Zee J, Engelborghs, S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens Krist'l, De Deyn PP, Kumar-Singh S, Van Broeckhoven C, Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21, Nature, 442, 920-924, 2006 (times cited 733) 5. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M. Classification of primary progressive aphasia and its variants. Neurology 76, 1006-14, 2011 (times cited 823)

Abstract Degenerative neurological diseases

Worldwide 44.8 million people suffer from dementia, with Alzheimer’s disease as the principal cause in 70% of these cases. One out of five women aged 60 will develop Alzheimer’s disease (AD) over their further life course and one out of 7 men. Currently available medical treatment has limited efficacy and since 2002 no novel drugs have been approved for this disease. More recently, radioisotopes that measure the biological processes in the human brain in AD in vivo have revolutionized the scientific approach to AD and are having a significant impact on the way clinical trials for novel drug development are currently conducted. This will be illustrated by the example of the FDA and EMA approved amyloid tracers 18F-flutemetamol (Vizamyl, GEHC), 18F-florbetaben (NeuraCeq, Piramal Imaging) and 18F-florbetapir (Amyvid, AVID). The hurdles to implementation in clinical practice will also be discussed. Finally, we will briefly describe highly promising radioisotopes at the proof-of-concept stage in Alzheimer disease and frontotemporal degeneration.

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Serge Goossens CEO ISI President EITA

Serge Goosssens was born on 31/12/1956 in Wilrijk. He started in 1983 as an independent carrier of radioactive material. In 1986, he founded ‘Expres vervoer bvba’, the firm that transformed in the 90’s to ‘Isotopes Services International NV’ of which Serge is currently majority shareholder and managing director. In 1998, he was co-founder of EITA, European Isotopes Transport Association, of which he’s the current president. He’s member of AIPES. Serge is also co-founder and shareholder of Isovital France, a transport company specialised in medical radioactive material.

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Kristoff Muylle President EANM

Dr. Kristoff Muylle graduated as M.D. from the University of Brussels (VUB) in 1999 and as Nuclear medicine physician in 2004. He was Senior Staff Member of the Department of Nuclear Medicine at the Jules Bordet Institute in Brussels. He now heads the Department of Nuclear Medicine at Sint-Jan Brugge-Oostende AV, Campus Henri Serruys in Ostend. Dr. Kristoff Muylle is President of the European Association of Nuclear Medicine (EANM) and Past- President of the Belgian Society of Nuclear Medicine (Belnuc). His fields of expertise and research interest are nuclear medicine applications in hemato-oncology, in particular FDG-PET, immuno-PET and radioimmunotherapy.

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Abstract poster

Hybrid gold nanoparticles coated with organic polymers and antibodies as platform for cancer theranostics: Cytotoxicity assessment

Authors N. Daems(1)(2), R. Marega(3), O. Fichera(3), S. Cagno(4), K. Van Hoecke (4), S. Baatout(1) , T. Cardinaels (4), C. Michiels(2), S. Lucas(3) and A. Aerts(1)

Affiliations (1) Radiobiology Unit, Institute for Environment, Health and Safety, SCK•CEN, Belgian Nuclear Research Centre, Mol, Belgium (2) Unité de Recherche en Biologie Cellulaire (URBC)-NARILIS, University of Namur, Belgium (3) Laboratoire Analyses par Réactions Nucléaires (LARN), Centre de Recherche en Physique de la Matière et du Rayonnement (PMR)-NARILIS, University of Namur, Belgium (4) Radiochemistry expert group, Institute for Nuclear Materials Sciences, SCK•CEN, Belgian Nuclear Research Centre, Mol, Belgium

Cancer is among the leading causes of mortality worldwide. Currently, the conventional therapeutic approaches are surgical removal combined with chemo- and/or radiotherapy. However, despite the recent advances in cancer therapy, a significant number of patients still experience tumor recurrence and have serious side effects due to damage to the healthy tissues. Therefore, there is a need to develop new strategies that allow a more efficient cancer cell killing, while sparing surrounding healthy tissues (1). In cancer radiotherapy, gold nanoparticles have emerged as promising radiosensitizers, which accumulate in the tumor and are believed to increase the effectiveness of external beam radiotherapy by local production of reactive oxygen species (ROS) and secondary electrons upon irradiation. At UNamur, 5 nm gold nanoparticles surrounded by an organic shell of polyallylamine are produced by plasma vapour deposition and are conjugated to anti-EGFR-antibodies (Cetuximab) for active tumour accumulation (mAb-AuNPs@PPAA) (2). Previous studies demonstrated that the mAb-AunPs@PPAAs actively target EGFR overexpressing tumour cells both in vitro as well as in vivo (3-4). Besides tumor uptake, in vivo biodistribution studies have demonstrated a significant accumulation of the mAb- AuNPs@PPAA in liver and spleen. Furthermore, the route of excretion is via the kidneys and bladder. Therefore, the cytotoxicity profile of the gold nanoparticles should be investigated properly in these healthy cell types prior to use the mAb-AuNPs@PPAA in clinical applications. In this project, human kidney cells (HK-2 cell line) and telomerase-immortalized microvascular cells (TIME cell line) were studied as first examples of healthy cells. In parallel, EGFR-overexpressing epidermoid cancer cells (A431 cell line) and EGFR-low expressing breast cancer cells (MDA-MB-453 cell line) were used as respectively positive and negative controls for antibody-targeting. We performed MTS tetrazolium cytotoxicity assays after 3 hours of nanoparticle incubation and live cytotoxicity imaging during 72 hours of nanoparticle incubation. The nanoparticle concentrations tested ranged from 8 μM to 253.85 μM of gold.

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In the future, we will also assess cellular gold uptake by ICP-MS and TEM, DNA damage using y-H2AX staining and perform ROS measurements. Finally, this part of the project should be finalized by repeating the experiments using primary cells.

References (1) Li S, et al. Nanotechnology. 2016;27(45) (2) N. Moreau, et al. Plasma Process Polym. 2009; 6, S888-S892 (3) Marega R, et al. J Mater Chem. 2012;22(21305) (4) Karmani L, et al. Contrast Media Mol Imaging. 2013;8(5):402-8

Acknowledgements N Daems is supported with a 2-years FRIA PhD grant of F.R.S-FNRS (National Fund for Scientific Research, Belgium).

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Abstract poster

213Bismuth-labeled nanobodies as a new treatment approach in Targeted Alpha Therapy

Authors Yana Dekempeneer1.2, Dominic Maertens1, Mireille Gysemans1, Tony Lahoutte2.3, Matthias D’Huyvetter2, Thomas Cardinaels1.4, Vicky Caveliers2.3.

Affiliations 1. Belgian Nuclear Research Center (SCK•CEN), Institute for Nuclear Materials Science, Boeretang 200, B-2400 Mol, Belgium 2. Vrije Universiteit Brussel (VUB), In vivo Cellular and Molecular Imaging Laboratory, Laarbeeklaan 103, B-1090 Jette, Belgium 3. UZ Brussel, Department of Nuclear Medicine, Laarbeeklaan 101, B-1090 Jette, Belgium 4. KU Leuven, Department of Chemistry, Celestijnenlaan 200F, P.O. Box 2404, B-3001 Heverlee, Belgium

The use of nanobodies (Nbs) as vehicles in targeted alpha therapy (TAT) has gained traction due to their excellent in vivo properties, high affinity and specificity, fast diffusion and clearance kinetics. Moreover, Nbs show good tumor penetration due to their small size. The main strength of TAT is the potential to deliver a high level of ionizing radiation in a localized manner because of the short range of alpha particles in tissue. In combination with a tumor-seeking vehicle, TAT could specifically eliminate isolated cancer cells, while causing little damage to healthy cells. The aim of this study is to develop a novel molecular targeted therapy that combines the -particle emitting radioisotope Bismuth-213 (213Bi) and the HER2-targeting 2Rs15d-Nb to selectively destroy HER2-positive metastases.

From an onsite 229Th source (1), the purified 225Ac is loaded on a pre-packed column containing AG MP-50 cation exchange resin. In dilute acid, both 225Ac and 213Bi are efficiently adsorbed to this cation exchange resin due to their stable 3+ oxidation state. 213Bi is selectively eluted from the cation - 2- exchange resin as anionic BiI4 /BiI5 species. Chemical separation experiments were performed on non-radioactive solutions (were La was used as simulant for Ac) to develop a reliable Ac/Bi separation methodology which will then be applied on radioactive 225Ac. Different bed volumes and eluents concentrations were evaluated. Inductively-coupled plasma mass spectrometry (ICP-MS) was used to evaluate the performance of the separation methodology. The final goal is to produce high purity 213Bi and minimize 225Ac breakthrough.

In a next step, 213Bi-labeled HER2-targeting 2Rs15d-Nbs will be developed. Therefore, classical diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’- tetra- acetic acid (DOTA) derivatives will be used as bifunctional chelator, conjugated to tumor-targeting 2Rs15d-Nbs on one hand and complexing 213Bi on the other hand. The different conjugates will be evaluated for their stability, binding specificity and immunoreactivity in HER2pos SKOV-3 cells. Due to

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the 46 min half-life of 213Bi, the 213Bi labeling reaction and quality control of 213Bi preparations must be performed in a very short time frame to avoid significant decay losses.

References (1) Boden, Sven, et al. "Thorium-229 quantified in historical Thorium-228 capsules." Applied Radiation and Isotopes 120 (2017): 40-44.

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Abstract poster

Producing 225Ac at CERN-MEDICIS via combined Resonant Laser Ionization and Mass Separation

Author Kristof Dockx1

Affiliation 1 Institute for Nuclear and Radiation Physics, KU Leuven, Celestijnenlaan 200D, 3001 Leuven, Belgium

To improve the effect and efficiency of cancer treatments, the interest for new radioisotopes in nuclear medicine has significantly grown over the past years. Alpha-emitting isotopes have a large potential to offer solutions, where other medical approaches cannot be used. Targeted Alpha Therapy (TAT) can be such solution. The alpha particles result in a high biological damage to local tumor cells and a very limited dose to the surrounding healthy tissue. Actinium-225 (225Ac) and its daughter Bismuth-213 (213Bi) are very promising alpha emitting radioisotopes. The availability of both 225Ac and 213Bi for research is however limited, hindering fast progress in the development of these new cancer treatments. Today, 225Ac isotopes used for research are milked from the decay of Thorium- 229 (229Th). This 229Th is a result of the research performed in the 20th century for civil and military applications. Other production methods use cyclotron irradiations of 229Th or 226Ra. However, all of these methods result in a batch of 225Ac with impurities like Actinium-227 and others. Purification of these batches require very difficult processes and cannot always guarantee a product that meets GMP standards. Therefore, the CERN-MEDICIS Collaboration is working on the development of a new technique to produce these highly promising medical isotopes. A new facility, CERN-MEDICIS [1], is under construction, which will provide dedicated medical batches for radiopharmaceuticals. It will extend the capabilities of the ISOLDE radioactive ion beam facility, operated with a 1.4 GeV proton beam and the on-line mass separator. The resonant laser ionization technique will be used for the element specific separation of the produced isotopes. Here, using a combination of laser beams with carefully selected wavelengths, a chemical separation can be achieved due to the difference in electronic resonant states of the chemically different isotopes. After the chemical selection, mass separation is applied on the produced beam to end up with an element and mass specific ion beam of 225Ac. After collection and the appropriate radiochemistry, this batch of pure radioisotopes is send to medical institutes for medical treatments.

References [1] dos Santos Augusto,R.M et al (2014). CERN-MEDICIS (Medical Isotopes Collected from ISOLDE): a new facility. Applied Sciences, 4:265-281

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Abstract poster

Cyclotron produced terbium radionuclides for theranostic applications

Authors Roberto Formento Cavaier1,2,3,4, Ferid Haddad1,3, Ilyes Zahi2, Thomas Sounalet1,3 , Thierry Stora4

Affiliations (1)SUBATECH, University of Nantes, 4 rue Alfred Kastler, Nantes 44000, France (2)Advanced Accelerator Applications, 20 rue Diesel, Saint-Genis Pouilly 01630, France (3)Arronax GIP, 1 rue Arronax , Nantes Cedex 44817 , France (4)CERN, 1211 Geneva 23, Switzerland

The interest in radiopharmaceuticals is in continuous growth, from the consolidated diagnostic applications, namely PET and SPECT, to the wide range of therapeutic applications with the use of different radionuclides. Furthermore during the last decade, the rising importance of theranostic concept focused the research towards the exploitation of new innovative radionuclides. Theranostic refers to the coupling of both diagnosis and therapy agents in order to go to the direction of the personalized treatment for each patients. Using the same vector for both imaging and therapy, it reaches the target organ in the same way and with the same efficiency. The aim of my work is to infer the feasibility of producing innovative radioisotopes for theranostic using a commercial middle sized high-current cyclotron while exploiting the technology of the mass separator developed within the MEDICIS-PROMED project; this will allow the production of high specific activity radioisotopes, not achievable with the common post-processing by chemical separation. MEDICIS-PROMED is a Marie Sklodowska-Curie innovative training network of the Horizon 2020 European Commission`s program, a wide project which covers all the aspects from the radionuclides production to the medical application passing through the collection, shipment, safety control and radiochemical synthesis, The first step of my work was to determine the radionuclides of interest for theranostic applications. A list of interesting radionuclides has been made evaluating the radiological properties for both imaging and therapy (half-life, decay and emission energy) as well as their chemical properties (i.e. labeling to peptides, antibodies). The most interesting one is terbium for its attractive quadruplet of radionuclides for medical applications: α-therapy, PET, SPECT, β-therapy: respectively Tb-149, Tb-152 Tb-155, Tb-161. Whereas for cyclotron production of Tb-152 and Tb-155 a natural Gadolinium target is adequate enough, for the production of Tb-149, the lightest alpha emitter, irradiation of enriched gadolinium is mandatory. A comparative study of the production from different enriched target isotopes is made considering the cross sections of the reactions of interest and the achievable yield for each of them, with the maximum available enrichment on the market. It results that the 67.1 % enriched Gd-154 target as the best potential target with a 70 MeV cyclotron proton beam. Next step will be the target preparation with electrodeposition process followed by experiments at the off-line facility at CERN in order to define the best setting parameters for terbium extraction from

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gadolinium targets. These elements will give the optimal parameters for the final experiment consisting firstly in the irradiation of a gadolinium target at Arronax cyclotron and mass separation at CERN-MEDICIS then. This research project has been supported by a Marie Skłodowska-Curie Innovative Training Network Fellowship of the European Commission’s Horizon 2020 Programme under contract number 642889 MEDICIS-PROMED.

References [1] R. Augusto, L. Buehler, Z. Lawson, S. Marzari, M. Stachura, T. Stora, CERN-MEDICIS (Medical Isotopes Collected from ISOLDE): A New Facility, Applied Science 2014, 4, 265-281, ISSN 2076-3417.

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Abstract poster

Analysis of Laser Resonance Ionization of Lutetium for the MEDICIS project

Authors V. Gadelshin, R. Heinke, T. Kieck, P. Naubereit, D. Studer, and K. Wendt

Affiliation LARISSA workgroup, Institute of Physics, University of Mainz, Staudingerweg 7, D-55128 Mainz, Germany

The MEDICIS project aims for the development, production, and application of innovative radiopharmaceuticals for radionuclide therapy and functional imaging. The project is carried out in a broad collaboration of various European academic, scientific, medical, and business institutions, and will involve the future CERN-MEDICIS facility for medical radioisotope production [1]. A dedicated laboratory is under construction adjacent to the existing CERN-ISOLDE radioactive ion beam facility, and is based on the same concept – Isotope Separation On-Line. From the multitude of different isotopes, generated by bombardment of a target material with 1.4 GeV proton beam, the desired medical radionuclide must be extracted with highest purity and efficiency.

To achieve these requirements, the resonance ionization laser ion source (RILIS) technology combined with a conventional electromagnetic separating unit is going to be implemented. Through a multi-step laser resonant excitation process, atoms of only the desired element will be driven into an auto-ionizing state, leading to high ionization probability and selectivity, with the subsequent isotope separation of ionized atoms [2]. Identification and characterization of a specific multi-step laser resonant excitation scheme is required to provide the most efficient ionization process.

One of the demanded medical radionuclide in the world is lutetium-177. Because of its high relevance, laser resonance ionization spectroscopy has been accomplished firstly on lutetium. The spectroscopy was carried out using of wide-range tuneable pulsed Titanium:sapphire lasers, which are supposed to be a core of the MEDICIS laser system. For the first time, various appropriate twostep UV-red excitation schemes of lutetium have been investigated. A comparison survey with the data of previous work has been undertaken [3]. Analyzing the results of ionization efficiency measurements, a highly efficient and highly selective excitation scheme for lutetium has been chosen. In the report, the study of two-step laser resonance ionization of lutetium are presented.

References 1. dos Santos Augusto R. M. et al.: CERN-MEDICIS (Medical Isotopes Collected from ISOLDE): a new facility. Applied Sciences, 4, 265 (2014) 2. Letokhov V. S.: Laser photoionization spectroscopy. Academic Press, Orlando: 353 pages (1987) 3. Gadelshin V. et al.: Laser resonance ionization spectroscopy on lutetium for the MEDICIS project. Hyperfine Interactions, 238(1), 28 (2017)

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Abstract poster

Separation of radium and actinium from historical Th-229 sources for production of radioisotopes for targeted alpha immunotherapy

Authors Dominic Maertensa, Mireille Gysemansa, Wendy Mentensa, Yana Dekempeneera,b, Thomas Cardinaelsa,c

Affiliations a Belgian Nuclear Research Centre (SCK•CEN), Boeretang 200, B-2400 Mol, Belgium b Vrije Universiteit Brussel (VUB), ICMI lab, Laarbeeklaan 103, B-1090 Brussel, Belgium c KU Leuven, Department of Chemistry, Celestijnenlaan 200F, P.O. Box 2404, B-3001 Heverlee, Belgium

Three historical sources containing a complex mixture of Th-229, Th-228, Ac-227, Ra-226 and their short-lived decay products were analyzed with high-resolution gamma spectroscopy in 2015.(1) As an important amount of Th-229 was quantified, in combination with an increased awareness of the potential therapeutic applications of the alpha emitters Ac-225 and Bi-213, the SERAPHIM (Separation of radium and actinium from historical Th-229 sources for production of radioisotopes for targeted alpha immunotherapy) project was launched in 2016 with the aim to open these sealed capsules, dissolve the content, and isolate the respective radioisotopes of interest.

The main objective of the SERAPHIM project is therefore to obtain a pure Th-229 source at SCK•CEN, that can assure a constant supply of Ac-225 and Bi-213 for (1) pre-clinical R&D in the field of targeted alpha immunotherapy (TAT) and all its related aspects (2) chemical separation R&D, i.e. development of Ac-225/Bi-213 generators, and development of Ra- 226 separation and conversion chemistry using Ra-225/Ac-225 tracers

The historical Th-229 source with the lowest dose rate and lowest amounts of Ac-227 and Ra-226 was selected to isolate the first pure Th-229 fraction. A specific glove box was used to safely execute the recovery process. Chemical separation experiments based on extraction chromatography were performed in advance on simulated solutions to develop a reliable Th/Ac/Ra/Pb separation methodology which was applied on the real historical Th-229 source.

Gamma spectroscopy measurements revealed that the first acid leach and consecutive chemical separation process was successful and already recovered the majority of Th-229, while a second acid leach and consecutive chemical separation process was needed to recover the remaining amount of Th-229. Mass balance calculations were performed to calculate the recovery yield of the full process. The first recovery of pure Th-229 provides valuable input for the processing of the two remaining capsules containing higher amounts of Th-229, Ac-227 and Ra-226.

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References 1 “Thorium-229 quantified in historical Thorium-228 capsules”, Simone Cagno, Dominic Maertens, Sven Boden, Koen Vints, Karen Van Hecke, Thomas Cardinaels, Applied Radiation and Isotopes volume 120, page 40–44

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Abstract poster

A type B container for the transport of isotopes for medical purpose: design’s strategies and shielding characterization

Authors M. Maietta(1,2), S. Avila(2), A. Cadiou(1), F. Haddad(1,3)

Affiliations 1. SUBATECH, 4 rue Alfred Kastler La Chantrerie, BP 20722, 44307 Nantes cedex, France. 2. LEMER PAX, 72 rue de Lorraine, zone d’Activite Erdre Active-Malabry, 44240 La Chapelle sur Erdre, France. 3. GIP ARRONAX, 1 rue Arronax, F-44817 Nantes Cedex 3, France.

Transportation of high activities of innovative radioisotopes from the production sites (e.g. the CERN- Medicis facility and the ILL reactor) to hospital’s radio-pharmacy or laboratories is the main frame of this work. The activity thresholds for the non-conventional isotopes given by the current European regulation (A1 and A2 limit) imply that a special type of container, classified as Type B, has to be used for transportation. Different type B containers exist but our goal is to design one dedicated to radionuclides used in nuclear medicine and with an affordable price. The design consists in different phases aiming to formally demonstrate the satisfaction of the legal requirements and strict rules described by the International Atomic Energy Agency (IAEA) [1]. The first phase consists in the specification of the radionuclides to be transported and in the identification of the radioprotection constraints. The dimensioning and the choice of the shielding materials have been performed with a Monte Carlo Code (MCNPX) aiming to predict the radiation level at the contact with the package. The need to transport radioactive beta emitter isotopes (e.g. Y90, Lu177, Sm153) poses the safety problems arising from the potential exposure of the workers to radiation coming from Bremsstrahlung effect. Part of this work consisted into the research of the strategy, in terms of choice of the materials and relative thicknesses, to minimize this effect. On the other hand some typical isotopes emit also high-energy gammas. One example is the Na24, with its 1.4 and 2.7 MeV gammas, generally present on the aluminum packaging around the ampoules used to irradiate material on reactor sites. The materials’ study goes in parallel with the consequences on weight and dimensions of the package. The second phase consists in a virtual testing, aiming to prove the performance of the chosen design and of the protection in normal and accidental conditions. It is performed with the software ANSYS. The final stage lies on a prototype realization with real tests, like drop test, fire exposure and water immersion. This PhD project is part of the "MEDICIS-produced radioisotope beams for medicine", a Marie Sklodowska-Curie Innovative Training Network of the Horizon 2020 EU program (Grant agreement No. 642889).

References [1] Regulations for the Safe Transport of Radioactive Material, 2012 Edition - Specific Safety Requirement No. SSR-6 6th Symposium on Medical Radioisotopes page 51 of 58 SCK•CEN/22527775 ISC: Public

Abstract poster

CERN-MEDICIS: A new facility for the production of innovative medical radioisotopes

Authors N.-T. Vuong1, A.-P. Bernardes1, T. Stora1

Affiliations 1 CERN, Meyrin, Switzerland

The CERN-MEDICIS facility aims at providing partners hospitals and research centers with the next generation of medical isotopes. Since different radioisotopes can emit different particles, combinations of isotopes from the same chemical element can be used in diagnostic imaging (PET, SPECT) and therapy of cancer (alpha, beta, Auger). The production of non-conventional medical isotope will mark the entrance of CERN into the era of theranostics. This growing oncological field allows to quantifying the presence of cancer cells in a given patient with the diagnostic radioisotope, before treating the disease with the therapeutic radioisotope.

MEDICIS-Promed, a Marie Sklodowska-Curie Innovative Training Network of the Horizon 2020 EU program will train a new generation of 15 entrepreneurial scientists to advance the applications of radioisotopes in nuclear medicine. The network objectives include the development of: i) the CERN- MEDICIS facility; ii) the 11Carbon PET-aided hadron therapy; iii) the synthesis of radiopharmaceuticals for diagnostic imaging and cancer therapy.

The MEDICIS isotope production process is based on the ISOL (Isotope Separator On-Line) technique developed at CERN-ISOLDE for over 40 years. In this facility, high energy proton beam are shot on a solid target material which generates hundreds of different isotopes by nuclear reactions. Newly produced species are extracted, ionized and accelerated to form a secondary radioisotope ions beam. This beam is then mass separated by an electromagnet and isotopes are implanted on a metallic foil. Samples of radioisotope batches will be used as starting material for further chemical separation processes in the future CERN-MEDICIS Radiochemistry Laboratory. Thus, purified radioisotopes will be dispatched to surrounding research centers to perform further studies in the area of nuclear medicine.

Current, radionuclides of interest are including but not limited to: Sc-44, Sc-47, Cu-61, Cu-64, Cu-67, Tb-149, Tb-152, Tb-155, Tb-161, Ac-224, and Ac-225.

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Abstract poster

Visual reading of amyloid-PET in MCI challenged: should we consider alternative methods?

Authors Jolien Schaeverbeke1,2, Kate Adamczuk1,2, Karolien Goffin3, Rose Bruffaerts1,5, Jos Tournoy, Ronald Peeters4, Koen Van Laere2,3, Rik Vandenberghe1,2,5

Affiliations 1Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Belgium 2Alzheimer Research Centre KU Leuven, Leuven research Institute for Neuroscience & Disease, University of Leuven, Belgium 3Department of Nuclear Medicine & Molecular Imaging, University Hospitals Leuven, Belgium 4Radiology Department, University Hospitals Leuven, Belgium 5Neurology Department, University Hospitals Leuven, Leuven, Belgium

Principal investigator: Prof.dr. Rik Vandenberghe

Background: Visual assessment of amyloid PET scans is considered the gold standard in clinical practice, although semiquantitative methods might be more sensitive to detect amyloid burden in a preclinical population (Adamczuk et al., 2016). Objective: Evaluate the concordance between visual assessment and a semiquantitative method in measuring amyloid burden in Mild Cognitive Impairment (MCI) patients. Methods: A consecutive series of 38 amnestic MCI patients (71 ± 6.5 (55-83) years, MMSE 28.2 ± 1.5 (25-30), symptom duration at study entry = 4.5 ± 3.2 (1-17) years) underwent 18F-florbetaben PET 90-120 min p.i, with an injected dose = 282 ± 43 MBq (113-316 MBq). The 6x5min frames were realigned and summed using SPM12. The resulting sumPET images were visually assessed by three independent, blinded, certified readers for amyloid positivity. Agreement between readers was analyzed using Fleiss kappa. SumPET images were also analyzed using a semiquantitative method to obtain Standard Uptake Volume Ratio (SUVR) with cerebellar gray matter as reference region. To calculate a SUVR neocortical composite value, VOIs were derived from the Automated Anatomical Labelling atlas and masked with the subject-specific GM map thresholded at 0.3. A neocortical SUVR composite threshold was determined in an independent 18F-florbetaben PET dataset consisting of 17 controls and 17 Alzheimer dementia patients using a previously published method (Vandenberghe et al., 2010). Results: Positive visual reads were obtained in 8 out of 38 MCI cases (MCI due to AD), while the remaining 30 were considered visually negative on amyloid burden (non-AD MCI). Observed agreement between readers was higher than chance but still lower than expected (Fleiss kappa = 0.66 ± 0.09 (95% CI: 0.61-0.71), p < 0.001). Six of the cases who were classified as negative based on the visual read, were classified as amyloid positive based on the semiquantitative threshold. No discordant cases were found in the visually assessed amyloid positive group (Figure 1).

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Conclusion: 21% vs. 37 % of MCI cases were amyloid-positive based on visual reads versus semiquantitative assessment, respectively. Semiquantitative methods might thus be more sensitive to detect amyloid burden in a mild disease stage compared with standard visual assessment.

Figure 1. 18F-florbetaben PET Imaging in amnestic MCI: Concordance between semiquantitative and visual assessments.

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Abstract poster

Large scale production of 11C for PET-aided hadron therapy

Authors S. Stegemann1, T.E. Cocolios1, T. Stora2

Affiliations (1)KU Leuven, Institute for Nuclear and Radiation Physics, Celestijnenlaan 200d, 3001 Heverlee, Belgium (2)CERN, 1211 Geneva 23, Switzerland

Hadron therapy, and particularly carbon therapy, is a very precise treatment for cancers with localized tumors. However, such treatments rely on complex treatment planning systems that simulate the dose delivery to the patient. Deviations or complications during treatment, caused e.g. by moving organs, can seriously harm the neighboring healthy tissue. On-line or post-treatment dose verification is complex and cannot image the exact position where energy is deposited. Therefore, we are developing a carbon-11 based hadron therapy protocol, which combines the treatment of cancer with accurate on-line PET-imaging of the irradiation field. By replacing stable carbon with 11C, 3D dose distributions of the exposed tissue can be measured during treatment, verifying the dose that is delivered to the patient. Carbon-11 is a known beta-plus emitting radioisotope, widely used in imaging techniques in nuclear medicine. The on-site batch mode production involving compact low-energy cyclotrons and nitrogen gas targets is a well-established process. However, the challenge of using a radioactive ion beam for treatment is to deliver the beam continuously in pure and sufficient intensity to the patient (~ 4∙108 ions/s). Considerably large losses during beam preparation and transport are inevitable, implying a large scale isotope production. Therefore, we propose a production system based on the ISOL method (Isotope Separation On-Line), which will allow to produce 11C in desirable quantity and purity. This technique includes the primary irradiation of a solid target by a low-energy proton beam, followed by isotope extraction, transport, ionization and mass separation. Correspondingly, studies of the target material, optimal ion source and transport systems are conducted. Outcome will be a compact production unit, adaptable to existing hadron facilities. This research project is carried out within the framework of the MEDICIS-Promed Marie Curie training network, which is dedicated to the production of novel radioisotopes for medical application.

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Abstract poster

Purification of medical 153Sm using radiation-resistant ionic liquids

Authors Michiel Van de Voordea,b, Karen Van Heckea, Simone Cagnoa, Thomas Cardinaelsa,b, Koen Binnemansb

Affiliations a SCK•CEN, Belgian Nuclear Research Centre, Radiochemistry Expert Group, Boeretang 200, 2400 Mol, Belgium b KU Leuven, Department of Chemistry, Celestijnenlaan 200F, PO 2404, 3001 Leuven, Belgium

153Sm can be used as a radiopharmaceutical for treatment of bone metasteses via bone pain palliation - 153 because of its favourable physical decay properties (t1/2 = 46.284 h, β emitting radioisotope). Sm can also be used in bone imaging using γ-ray detectors because of γ-photons emission. 153Sm is usually produced via neutron irradiation of an enriched 152Sm target, i.e. 152Sm(n,γ)153Sm. However, 154 153 Eu (t1/2 = 8.593 y) is also formed in the targets by neutron capture of Eu, the decay product of 153Sm. By keeping the irradiation time short, the amounts of this impurity can be kept relatively low compared to the 153Sm activity, allowing the 153Sm to be used without purification from Eu. This is, however, associated with the drawback of a rather short shelf-life of the 153Sm product since the ratio of 153Sm/154Eu decreases significantly with time. To increase the availability and decrease the prize of the product, it would be beneficial if the shelf-life could be increased and/or the irradiation time could be prolonged. Therefore, the 154Eu has to be removed from the 153Sm. This, however, is not straightforward because of the very similar chemical properties of both neighbouring lanthanides and the low concentration of europium compared to samarium. Moreover, a separation method based on solvent extraction technology that could be automatized would be beneficial to minimize the dose rate for the operators. In this study, the use of radiation resistant ionic liquids (ILs) for the separation of the radiolanthanide pair 153Sm/154Eu is investigated. ILs are solvents that consist entirely of ions and they are a very interesting alternative for the molecular organic phase in solvent extraction processes. To prevent any losses of the IL, hydrophobicity of the IL is very important. Since the use of fluorinated ILs have to be prevented, both for radiolysis and waste treatment reasons (CHON principle), hydrophobicity was achieved via the cation using long alkyl chains. Besides, radiation resistivity of the IL is also a very important selection criterion. Therefore, the use of the IL benzyltrioctylammonium nitrate is investigated.

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