Preclinical Molecular Imaging Contents
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Department of Radiology · University of Tübingen Preclinical Molecular Imaging www.preclinicalimaging.org contents OUR MISSION 02 01 Non-invasive Small Animal Imaging – A New Approach in Biomedical Research 02 From Mouse to Man – from the Laboratory Bench to the Patient’s Bedside! 03 LABORATORY FOR PRECLINICAL IMAGING AND IMAGING 02 TECHNOLOGY OF THE WERNER SIEMENSFOUNDATION 04 Preclinical Imaging in Tübingen 04 Development of Funds and Human Resources 05 COOPERATIONS 06 03 Cooperation with Industry 06 Academic Cooperations 07 Partners in Tübingen 07 External Partners 07 INFRASTRUCTURE 08 04 Imaging Equipment 08 Animal Holding and Hygiene Concept 09 Image Analysis 09 Surgical Interventions 09 Physiological Monitoring 10 Translational Imaging 10 Radiopharmacy Unit 10 Our Technological Development Pioneers Molecular Imaging 11 In Vivo meets In Vitro 11 PROJECT EXAMPLES 12 05 Project Management and Study Workfl ow 12 Neurooncology & Neurodegeneration 13 Oncology 15 Imaging in Immunology 17 REFERENCES 18 06 References and Affi liations 18 Workshop for Small Animal Imaging 18 Example of Established Animal Models 19 Recent Important Publications 20 LOCATION 22 07 Scientifi c Environment & Culture 22 How to reach us 24 Contact Information 25 01 OUR MISSION non-invasive small animal imaging – a new approach in biomedical research Small animal imaging is an emerging fi eld which has an im- pact on various biomedical research areas such as neurology, oncology, cardiology, immunology and infection biology. Non-invasive imaging methods, such as magnetic resonance imaging (MRI) or positron emission tomography (PET) allow the direct in vivo quantifi cation of functional processes or metabolic rates in animal models using target or disease- specifi c biomarkers. Thus, imaging can replace time consum- ing and less reliable ex vivo and in vitro methods in many areas of biomedical science. The pharmaceutical industry will profi t from these tools as they accelerate drug and biomarker development by yielding more reliable in vivo results and cost-effective study designs, while at the same time smaller animal numbers are required. Consequently, the pharmaceutical industry can get its prod- ucts onto the market faster and impact positively on animal protection. Professor Dr. Bernd Pichler Chair Preclinical Imaging and Radiopharmacy 02 | OUR MISSION from mouse to man – from the laboratory bench to the patient’s bedside! The mission of the Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in vivo imaging. This endeavour is achieved by developing no- vel imaging technologies and by using innovative imaging probes and animal models to gain information about phy- siology and pathology in vivo. A close association with the University Hospital (UKT) enables translational research and early clinical studies and ensures a fast transition of know- how from the research laboratory to the patient’s beds. | 03 02 LABORATORY FOR PRECLINICAL IMAGING AND IMAGING TECHNOLOGY OF THE WERNER SIEMENS-FOUNDATION preclinical imaging in tübingen The Laboratory for Preclinical Imaging and Imaging Technol- ogy in Tübingen was established in 2005, when Dr. Pichler returned to Germany from the University of California, Davis, USA. With over ten years experience in small animal imaging, Professor Pichler has established a highly motivated, skilled team of biologists, physicists, chemists, physicians, technical assistants and lab managers. The lab utilises the latest technological infrastructure and sets the highest standards in hygiene, animal welfare and physiological monitoring of animals. A large number of es- tablished imaging protocols, standard operating procedures (SOPs), and data analysis tools guarantee reliable scientifi c results. The affi liated radiopharmacy unit supplies the tracers, ensur- ing the fl exibility for innovative research projects. The Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation is hosted within the newly founded Department of Preclinical Imaging and Radiophar- macy (Chair: Professor Pichler), one of the fi ve Departments within Radiology of the University Hospital of Tübingen. Overall, the laboratory is committed to maintaining the high- est standards in non-invasive small animal imaging. 04 | LABORATORY development of funds and human resources Since Prof. Bernd Pichler became head of the newly founded laboratory in 2005, it has developed from a small laboratory into a state-of-the-art facility for preclinical imaging. Our success is demonstrated by a steady increase in the number of publi- cations and the quality of the journals in which publications are being placed as well as the amount of funds raised and the growth and development of personnel. Funds raised in � (Million)* Personnel development 3.0 18 2.5 16 14 2.0 12 1.5 10 8 1.0 6 4 0.5 PhD students s PostdocsPostdoc 2 Technicianechnicians/Engineers/ s 0.0 0 AAdministratiodministration 2005 2006 2007200820092010 200200005 2006 2007 2008 2009 20201010 *status June 2010 | 05 03 COOPERATIONS cooperations with industry The laboratory is an academic facility of the Medical Faculty at the University of Tübingen which has several years of ex- perience in contractual research with pharmaceutical compa- nies. Our benefi ts from these cooperations are threefold: • Close links with pharmaceutical companies widen our sci- entifi c spectrum by opening up new research strategies and provide access to novel diagnostic medical and thera- peutic drugs. • Our researchers are exposed to the scientifi c work envi- ronment of companies, an important experience to foster their professional careers. • Finally, contractual research can lead to joint publications or, if the sponsor requires confi dentiality, to fi nancial sup- port giving us more fl exibility for our research by main- taining a good laboratory infrastructure and suffi cient manpower. The Laboratory for Preclincal Imaging is hosted within the Currently our laboratory maintains collaborative research Department of Radiology of the University Hospital of Tübin- with more than six major national and international phar- gen. This means: maceutical companies. i) Results from basic research can be transferred to clinical validation on a shortcut to Diagnostic Radiology, Nuclear Medicine, Neuroradiology, Internal Medicine or Radiation Oncology, to name just a few. ii) A specifi c care unit for medical trial volunteers allows tight supervision of study parameters. iii) The laboratory is backed by the University Hospital’s pro- fessional administration. 06 | COOPERATIONS academic cooperations partners in tübingen external partners • Institute of Medical Microbiology and Hygiene • Max Planck Institute for Biological Cybernetics, (Prof. Autenrieth) Tübingen, Germany • Department of Radiation Oncology (Prof. Bamberg) • University of Münster, Germany • Department of Nuclear Medicine (Prof. Bares) • University Hospital Heidelberg, Germany • Department of Diagnostic and Interventional Radiology • University of Freiburg, Germany (Prof. Claussen) • Technische Universität München, Germany • Department of Diagnostic and Interventional • University of Erlangen-Nürnberg, Germany Neuroradiology (Prof. Ernemann) • University of Mannheim, Germany • Core Laboratory for Mouse Pathology (Prof. Fend) • University of Magdeburg, Germany • Department of Cardiology and Cardiovascular Medicine (Prof. Gawaz) • Swiss Federal Institute of Technology Zurich, Switzerland • University Children’s Hospital (Prof. Handgretinger) • Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie (IKP), Stuttgart, Germany • Department of General, Visceral and Transplant Surgery (Prof. Königsrainer) • Max Planck Institute for Physics, Munich, Germany • Department of Tropical Medicine (Prof. Kremsner) • University of California, Davis, USA • Department of Molecular Biology (Prof. Nordheim) • Stanford University, California, USA • Department of Immunology (Prof. Rammensee) • Universität Innsbruck, Austria • Microarray Facility (Prof. Rieß) • Paul Scherer Institute, Villigen, Switzerland • Department of Dermatology (Prof. Röcken) • Eindhoven University of Technology, Netherlands • Interfaculty Institute for Biochemistry • University of British Columbia, Canada (Prof. Feil, Prof. Schulze-Osthoff) • Department of Urology (Prof. Stenzl) • Department of Toxicology (Prof. Schwarz) | 07 04 INFRASTRUCTURE imaging equipment The laboratory offers 245m2 of restricted imaging and animal holding area with elevated hygiene. This entire sector is equipped with the latest air conditioning technology and HEPA fi lters. Personnel enter the restricted area in clean room wear through an air shower. The laboratory has been approved for bio safety level 2 (S2) work and as a radiation area, enabling the use of all major open radioactive isotopes for PET and SPECT imaging. The entire division consists of 350m2 lab space and 207m2 offi ce space. EQUIPMENT OVERVIEW • 2x Inveon dedicated PET scanners (Siemens) • 1x Inveon SPECT/CT (Siemens) • 1x µCT (Siemens) • 1x 7 Tesla MRI – ClinScan (Bruker) • Optical Imaging System (Hamamatsu) • Human PET/MR • Animal PET/MR 08 | INFRASTRUCTURE animal holding and hygiene concept Our newly built and extended animal imaging facility is run at an elevated hygiene status. The animal holding facilities utilize isolated ventilated cages (IVC) and are integrated within the animal imaging unit. To maintain a high hygiene status and avoid