Preclinical Molecular Imaging Contents

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 SIEMENS FOUNDATION 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 impact 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 novel imaging technologies and by using innovative imaging probes and animal models to gain information about physiology 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 established imaging protocols, standard operating procedures (SOPs), and data analysis tools guarantee reliable scientifi c results.

The affi liated radiopharmacy unit supplies the tracers, ensuring 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 highest 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 publications 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 Technicians/Engineerechnicians/ s 0.0 0 AdministratioAdministration 2005 2006 2007200820092010 200200005 2006 2007 2008 2009 20102010 *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 experience in contractual research with pharmaceutical companies. Our benefi ts from these cooperations are threefold:

• Close links with pharmaceutical companies widen our scientifi c spectrum by opening up new research strategies and provide access to novel diagnostic medical and therapeutic drugs.

• Our researchers are exposed to the scientifi c work environment 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 support giving us more fl exibility for our research by maintaining 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 professional 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 any contamination of the animals by personnel, we require that people wear dedicated lab clothes, face masks and hairnets as well as dedicated shoes. The air conditioning is laid out to support this high hygiene status and, in addition, we have an air shower and a sluice through which all people and materials must pass.

image analysis

A large amount of effort is being invested to provide high -end imaging analysis tools and procedures. We put special emphasis on using well tested and approved imaging analysis software like Inveon Research Workplace (Siemens Healthcare, USA) and PMOD (PMOD, Switzerland). PMOD is our default analysis tool for pharmacokinetic modelling as well as analysis of fused images. Our lab tests all the applied software tools in depth and is in regular contact with the R&D teams of Siemens and PMOD. Furthermore, our lab has developed dedicated software tools, especially for data archiving and data reporting. All imaging data including the large list mode fi les are stored in our facility in three different locations on a RAID system as well as on additional external hard drives. surgical interventions

Our animal imaging unit integrates a room for surgical interventions where we have a all the equipment available for surgeries in mice and rats. This includes a microscope, ste- reotactic holders for brain surgery and high precision drills. Furthermore, this room is equipped with surgical lamps, an exhaust fume hood as well as an isofl urane anesthesia system and warming pads to maintain and control the animals’ physiology during anesthesia. | 09 physiological monitoring translational imaging

High quality and reliable animal imaging demands the well- The Laboratory for Preclinical Imaging and Imaging Technol- being of the animals as well as a tight monitoring of physi- ogy not only focuses on small animal imaging, but also pro- ological parameters and maintenance of body temperature. vides infrastructure for large animal studies using our high Our laboratory is therefore equipped with dedicated custom- resolution brain PET/MRI scanner (Siemens Healthcare, USA) made animal beds allowing the temperature monitoring as as well as a clinical wholebody PET/CT scanner, 3 Tesla MRIs well as maintaining the body temperature of our animals. We or latest clinical CT scanners. The laboratory within the De- apply monitoring equipment for ECG, respiration, sO2, blood partment of Radiology has full access to these tomographs. pressure and blood gases. Furthermore, our laboratory regularly exchanges physicians and scientists with the Department of Diagnostic and Inter- ventional Radiology to maintain highly qualified staff, co- trained in basic research as well as in clinical radiological and nuclear imaging. Therefore, our laboratory can provide the studies in close collaboration with the Department of Inter- ventional and Diagnostic Radiology ensuring data acquisi- tion and study planning which allow truly translational studies from mouse to man.

radiopharmacy unit

The affiliated Radiopharmacy unit (Chair: Prof. Pichler) provides more than 20 established clinical-grade PET tracers for patient care and basic research. A 16 MeV cyclotron along with several 11C and 18F synthesis units and a good manufac- turing practice (GMP) facility form the basis for tracer production as well as for novel biomarker development. Beside the regular targets for 11C, 13N, 15O and 18F, our facility provides an in-house developed solid target for the production of 64Cu, 86Y and 124I. For further information, please consult the dedicated Radiopharmacy brochure.

10 | infrastructure our technological in vivo meets in vitro development pioneers molecular imaging In vitro validation of the imaging results remains essential. Thus, our laboratory is equipped with all standard in vitro and ex vivo analysis tools, such as The laboratory not only performs innovative biomedical research but also pioneers the next generation of novel im- • Blood gas analysis aging technology. Prof. Pichler’s group are leaders in the development of combined preclinical and clinical PET/MRI. • ELISA Furthermore, our group is internationally recognized for • RT-PCR achievements in developing novel detectors for next gen- • BLOT technology eration PET scanners. We focus on compact semiconductor based sensors such as avalanche photodiodes (APDs) or Gei- • Autoradiography ger mode APDs (G-APDs) connected to very fast, low noise • Gamma counting electronic circuits. • Immunohistochemistry

• and many more…

Three strictly separate cell culture labs for human, murine and transfected cells, along with regular established myco- plasma tests, reduce the risk of bacterial cross-contamination between cell lines.

| 11 05

PROJECT EXAMPLES

project management and study workflow

The chart below describes a typical study workfl ow contain- ing clearly predefi ned milestones which will be supported SCIENTIFIC AREAS by project review meetings. An allocated project manager with experience in preclinical and translational research will • Neurooncology & Neurodegeneration be the responsible contact throughout the entire study. The • Oncology project will be accompanied by regular teleconferences and • Imaging in Immunology exchange meetings to discuss results. This tight organisation • Morphological, Anatomical & ensures successful project workfl ows and identifi es problems Functional Imaging at a very early stage. • Imaging in Cardiology • Infectious Diseases 1

Project Idea Project Planning Ethical Approval

• Allocation of Project Manager Phase • Cost Calculation 2 Data Review Pilot Study Data Analysis Meeting

Phase • Regular T-Cons • Personal Meeting 3

Planning of Adapting Ethical Main Study Data Analysis Main Studies Protocols • Regular T-Cons Phase • 1-2 Meetings 4

Data Review Summarizing Meeting of Results Phase

12 | Project examPles neurooncology & neurodegeneration

PET/MR Oncology – Murine Astrocytoma Tumors ] This project focuses on combined multimodality imaging of 3 brain tumors using PET and MR. The metabolic function of brain tumors is evaluated by different PET tracers such as [11C]Choline, [18F]FLT and [11C]Methionine that depict parameters such as membrane activity, proliferation and amino Tumor volume [mm Tumor acid metabolism. Other functional and anatomic tumor parameters are generated via MR imaging which allows a determination of the tumor tissue permeability, assessment of tumor metabolites via MR spectroscopy, characterizations Days after tumor implantation of necrotic areas by use of diffusion weighted imaging and determination of tumor volume via anatomical MR imaging. The graph above shows the tumor volume of murine astro- The data obtained from PET and MRI are evaluated on an cytomas as a function of time after implantation. The volu- overall scale to gain insight into tumor metabolism. These me was determined using non-invasive MR imaging, thus in vivo imaging methods are complemented by ex vivo data allowing a clear determination of the tumor size at multiple such as histology. time-points in the same animals.

| 13 In vivo PET Quantification of the Dopamine Receptors and Transporters in Mice

Parkinson’s disease is characterized by a progressive degener- of interest in the brain and the activity over time is calculated. ation of nigrostriatal dopaminergic neurons. PET has become a To determine receptor and transporter binding parameters, powerful tool for receptor and transporter quantification and reference tissue models have become a valuable tool in brain has been used to study pathophysiology and disease progres- studies of rats and mice without the need for an arterial input sion over time, as well as therapeutic effects in different animal function from invasive arterial blood samples. models of neurodegenerative diseases. The reduction in striatal dopamine transporter binding, a measure of presynaptic dop- The binding potential (BPND) can be estimated from the Lo- aminergic integrity, is established with [11C]methylphenidate, gan graphical analysis using a linear regression equation of a radiotracer with a high affinity to the dopamine transporter. the target and the reference region. The distribution volume Changes in dopamine receptor density can be evaluated with is calculated by the slope of the linear part of the plot and is 11 11 [ C]raclopride, a radiotracer specific to 2D -receptors and [ C] equal to BPND+1.

SCH-23390, a radiotracer specific to 1D -receptors. For PET image quantification, regions of interest are drawn over an area

14 | Project Examples oncology

Antibody Targeting of Prostate Cancer

Despite recent improvements in early detection and treatment, prostate cancer continues to be the most common malignancy and second leading cause of cancer-related mortality in men in the western world.

The prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, is highly expressed by virtually all prostate cancers and represents an excellent candidate for targeting prostate cancer.

Shown here is the comparison of the [64Cu]DOTA labeled 3/A12 monoclonal antibody (mAb) with the new 3/F11 and 3/E7 radiolabeled mAb in SCID mice bearing human prostate tumors. Due to the high and specific uptake of the64 Cu-labeled mAb in PSMA-positive tumors, these ligands represent excellent candidates for prostate cancer imaging agents and poten- tially for radioimmunotherapy.

| 15 PET Biomarker Studies in Human Hormone- The aim of this study is to validate [11C]Choline, [18F]FEC and dependent Prostate Cancer Xenografted in [18F]FCh, three PET tracers specifically developed for pros- 18 Nude Rats tate cancer imaging, and to compare them with [ F]FDG and [18F]FLT pre- and post-surgical castration in a hormone- Clinical prostate cancer is a very heterogeneous disease; its dependent human prostate tumor model. behaviour ranges from indolent to aggressive states. Thus, imaging is challenging and the evaluation of new PET bio- Tracer uptake is analyzed by acquiring time activity curves markers is therefore important. (TACs), standard uptake value (SUV) and tumour-to-muscle- ratio (T/M). In addition, we measured the apparent diffusion The clinical “gold standard” in oncology PET is [18F]FDG. How- coefficient (ADC) and performed chemical shift imaging (CSI) ever for imaging prostate carcinoma (PCa) [18F]FDG is not of the xenogeneic nude rat model on a 7T MRI scanner. Imag- suitable as high bladder activity makes it difficult to differ- ing data are cross-correlated with molecular in vitro methods entiate between prostate, malignant tissue and the benign like immunohistochemistry and western blot. prostatic hyperplasia or inflammation. The tumor-bearing nude rat is a useful in vivo model to study The PET tracers mainly used for clinical prostate PET imaging new PET tracers for human prostate cancer diagnostic and are currently [11C]Choline and its derivates. As metabolism therapy efficacy monitoring. and membrane synthesis are elevated in the degenerated cells of the PCa, choline, a marker for membrane synthesis interacts with the malignancy-induced upregulated choline kinase alpha (ChK1).

Non-castrated Castrated

16 | Project Examples imaging in immunology

In vivo PET-Imaging of Inflammation and We use the GPI-arthritis model to evaluate hypoxia markers, Hypoxia gaining new insights into the molecular mechanisms which induce angiogenesis, hypoxia and eventually joint destruction. Auto-antibodies against Glucose-6 phosphate isomerase (GPI) induce arthritis in mice that closely resembles human We investigated the role of hypoxia-induced angiogenesis in rheumatoid arthritis (RA). Angiogenesis and hypoxia play a GPI arthritis non-invasively in vivo using 18F-fluoroazomycin- major role in organ-specific autoimmune diseases such as GPI arabinoside ([18F]FAZA) that selectively accumulates in hy- -arthritis. However, the exact mechanisms involved in neoan- poxic tissue. Established ex vivo molecular biology methods, giogenesis in RA remain enigmatic. such as real time PCR, autoradiography, western blot and histology were also used to cross-correlate and validate the in vivo results.

| 17 06

REFERENCES

references and affiliations

The laboratory conducts collaborative research with ma- workshop for jor pharmaceutical companies in Germany, Europe and the “small animal imaging” world. We serve as the European Training and Reference La- boratory for Preclinical Imaging of Siemens HealthCare. Prof. The laboratory organizes and conducts an annual workshop Pichler is a board member of the Academy of Molecular Ima- for Small Animal Imaging, a successful event held for the fi fth ging (AMI), council member of the Society of Molecular Ima- time in a row in Tübingen in 2010. ging (SMI) and the European Society for Molecular Imaging (ESMI), and heads the task force for preclinical molecular ima- The topics covered include: ging at the German Association for Nuclear Medicine (DGN). • Animal handling • microPET • microCT • microSPECT • 7 T MRI • Optical imaging • High-resolution ultrasound • Autoradiography, biodistribution, cell labelling, microscopy • Image analysis

18 | references example of established animal models

Animal Models in Oncology Animal Models in Neurology • Prostate – Xenograft • Alpha-Synuclein (Parkinson, mouse) –– PC-3 (nu/nu mouse) • 3 different Alzheimer models –– DU145 (nu/nu mouse) –– CWR22 (nu/nu mouse)

• Melanoma Animal Models in Immunology –– M21 • GPI-Arthritis (mouse) –– M21L • Contact allergy (TNCB, mouse) –– SKMEL28 • Contact allergy (OVA, mouse)

• Mamma – Endogenous –– PyV-mT (C57BL/6) –– PyV-mT (FVB) Experience in Imaging of other Animal Models in Cooperation with Companies • Colon –– CT26 • Colon – Xenograft: HCT116 • Lung – Xenograft: H460 • Pancreas – Endogenous (mouse) –– RIP1-Tag2 (C3H)

• Neuro-Oncology –– U87MG xenograft –– VM/Dk (SMA560)

• ... and many more

| 19 recent important publications

A.W. Sauter, H.F. Wehrl, A. Kolb, M.S. Judenhofer, B.J. Pichler: Combined PET/MRI: one step further in multimodality imaging. Trends Mol Med. 2010 Sep 17. [Epub ahead of print]

B.J. Pichler, A. Kolb, T. Nägele, H.P Schlemmer: PET/MRI: Pa- ving the Way for the Next Generation of Clinical Multimodali- ty Imaging Applications. J Nucl Med. 51(3):333-6, 2010

S. Nuber, T. Franck, H. Wolburg, U. Schumann, N. Casadei, K. Fischer, C. Calaminus, B.J. Pichler, S. Chanarat, P. Teismann, J.B. Schulz, A.R. Luft, J. Tomiuk, J. Wilbertz, A. Bornemann, R. Krüger, O. Riess: Transgenic overexpression of the alpha- synuclein interacting protein synphilin-1 leads to behavioral and neuropathological alterations in mice. Neurogenetics. 11(1):107-20, 2010

20 | Preferences M. Kneilling, R. Mailhammer, L. Hültner, T. Schönberger, K. M.S. Judenhofer, H.F. Wehrl, D.F. Newport, C. Catana, S.B. Sie- Fuchs, M. Schaller, D. Bukala, S. Massberg, C.A. Sander, M. Eich- gel, M. Becker, A. Thielscher, M. Kneilling, M. Lichy, M. Eichner, ner, K.L. Maier, R. Hallmann, B.J. Pichler, R. Haubner, M. Gawaz, K. Klingel, G. Reischl, S. Widmaier, M. Röcken, R.E. Nutt, H.- K. Pfeffer, T. Biedermann, M. Röcken: Direct Crosstalk between J. Machulla, K. Uludag, S.R. Cherry, C.D. Claussen, B.J. Pichler: Mast Cell-TNF and TNFR1-expressing Endothelia Mediates Lo- Simultaneous PET/MRI: A new approach for functional and cal Tissue Inflammation. morphological imaging. Blood. 114(8):1696-706, 2009 Nat Med. 14(4):459-65, 2008

U. Elsässer-Beile, G. Reischl. S. Wiehr, P. Bühler, P. Wolf, K. Alt, M. Kneilling*, L. Hültner*, B.J. Pichler*, R. Mailhammer, L. Mo- J. Shively, M.S. Judenhofer, H.J. Machulla, B.J. Pichler: PET ima- rawietz, S. Solomon, M. Eichner, J. Sabatino, T. Biedermann, V. ging of prostate cancer xenografts with a highly specific anti- Krenn, W. A. Weber, H. Ilges, R. Haubner, M. Röcken: Targeted body against the postate specific membrane antigen. mast cell cell–silencing prevents joint destruction and angio- J Nucl Med. 50(4): 606-611, 2009 genesis in experimental arthritis. Arth Rheum. 56(6):1806-1816, 2007 (*contributed equally) T. Wieder , H. Braumüller M. Kneilling, B. Pichler, M. Röcken: T cell-mediated help against tumors. B.J. Pichler, M. Kneilling, R. Haubner, H. Braumüller, M. Schwai- Cell Cycle. 7(19):2974-7, 2008 ger, M. Röcken, W.A. Weber: Imaging of delayed type hyper- sensitivity reaction by positron emission tomography and N. Müller-Hermelink*, H. Braumüller*, B. Pichler*, T. Wieder, R. [18F]Galacto-RGD. Mailhammer, K. Schaak, K. Ghoreschi, A. Yazdi, R. Haubner, C.A. J. Nucl. Med. 46(1):184-189, 2005 Sander, R. Mocikat, M. Schwaiger, I. Förster, R. Huss, W.A. We- ber, M. Kneilling, M. Röcken: TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell. 13(6):507-18, 2008 (*contributed equally)

| 21 07

LOCATION

scientific environment & culture

Tübingen is a traditional, historic university town situated on the Neckar river, 40 km southwest of Stuttgart on the fringe the Main research FocUs at the of the Swabian Jura mountains and the Black Forest. The city FacUlty oF Medicine is cUrrently on fi rst appears in offi cial records in 1191, however the town’s fortress dates back to 1078. The Eberhard Karls University is these areas: one of Germany‘s oldest universities, internationally recog- • Imaging and Medical Technology nized for medicine, theological sciences and the humanities. It was founded in 1477 by Count Eberhard V. • Infection Biology • Oncology and Immunology The closest major city is Stuttgart, located 40 km northeast • Neuroscience from Tübingen. Stuttgart, the capital of Baden-Württemberg • Vascular Medicine and Diabetes state, provides all the shopping and cultural lifestyle of a large city. It has a wide range of cultural offerings including museums, theaters and an operahouse. Scientifi c environment

Besides the university with its 14 faculties, Tübingen also has 17 hospitals affi liated with the University‘s Faculty of Medicine. In terms of third-party funds acquired, the number of Collaborative Research Centres, Graduate Programmes, Research Groups, plus its involvement in national and international collaborations, the Faculty of Medicine in Tübingen is rated one of the top ten Faculties of Medicine in all Ger- many’s accepted ranking lists.

22 | location Tübingen offers an unique scientific environment and host- ing institutions such as the Hertie Institute for Clinical Brain Research (HIH), which was established in Tübingen with pro- motional funds from the charitable Hertie Foundation. As a result of its close integration with the Department of Neu- rology and hence with the Centre for Neurology, it enables optimal coordination between basic research and medical applications.

Since October 2007, six faculties, the Max Planck Institute of Biological Cybernetics, the Hertie Institute for Clinical Brain Research, the Graduate School of Neural and Behavioural Sciences, and numerous internal and external partners have been participating in the Excellence Cluster “Interdisciplinary Centre for Integrative Neuroscience” (CIN). It is funded by the several close collaborations exist German Research Foundation (DFG), being one of the 20 Ex- cellence Clusters within Germany. between the University and the Max Planck Institutes located in Tübingen:

• Max Planck Institute for Biological Cybernetics • Max Planck Institute for Developmental Biology • Friedrich Miescher Laboratory

| 23 how to reach us

Due to the close proximity to Stuttgart, Tübingen is easily By plane: The nearest international airport is Stuttgart (code: reached by air. Stuttgart has a modern international airport STR). From the airport, you can reach our lab within 20 min with non-stop fl ights to and from major international des- by car or taxi. tinations. By train: You can reach our laboratory from Tübingen main You can reach Tübingen from the airport in about 20 min by station in 10 min by taxi or by bus line No. 5 in 7 min to the car. Public transport by bus or train is also available. stop “Uni-Kliniken Tal”.

By car: From the autobahn A8 (Munich-Stuttgart or Karlsruhe- Würzburg/ Heilbronn Stuttgart) via the exit “B27” near Stuttgart or from auto- Karlsruhe bahn A81 (Stuttgart-Singen) exit to Tübingen via “B28”.

Black Forest Laboratory

Tübingen

Swabian Alb

München

Singen Bodensee

24 | location contact information

Please visit our website www.preclinicalimaging.org to download a digital version of this brochure.

Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation Department of Preclinical Imaging and Radiopharmacy Eberhard Karls University Tuebingen Roentgenweg 13, 72076 Tuebingen Germany Prof. Dr. Bernd Pichler Chair Department of Preclinical Imaging and Radiopharmacy Phone: +49-7071-29-83427 Email: [email protected]

Dipl.-Biol. Uta Paulsen Account management, contracts Phone: +49-7071-29-83450 Email: [email protected]

Dr. Carsten Calaminus Project manager for neurology, oncology Phone: +49-7071-29-82972 Email: [email protected]

Dr. Valerie Honndorf Project manager for oncology Phone: +49-7071-29-87439 Email: [email protected]

Dr. Christian Kesenheimer Project manager for biomarker, radiochemistry Phone: +49-7071-29-87439 Email: [email protected]

Dr. Marcel Krüger Project manager for immunology, oncology Phone: +49-7071-29-82972 Email: [email protected]

Dr. Stefan Wiehr Project manager for infectious diseases, oncology Phone: +49-7071-29-83426 Email: [email protected]

| 25 Eberhard Karls University Tuebingen

Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation Department of Preclinical Imaging and Radiopharmacy Roentgenweg 13 · 72076 Tuebingen · Germany www.preclinicalimaging.org