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Preclinical Molecular Imaging Department of Radiology · University of Tübingen
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Page 1: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

Preclinical molecular imagingDepartment of Radiology · University of Tübingen

Page 2: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

www.preclinicalimaging.org

Page 3: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

OUR MISSION 02 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 TECHNOLOGY OF THE WERNER SIEMENS-FOUNDATION 04 Preclinical Imaging in Tübingen 04 Development of Funds and Human Resources 05

COOPERATIONS 06 Cooperation with Industry 06 Academic Cooperations 07 Partners in Tübingen 07 External Partners 07

INFRASTRUCTURE 08 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 Project Management and Study Workfl ow 12 Neurooncology & Neurodegeneration 13 Oncology 15 Imaging in Immunology 17

REFERENCES 18 References and Affi liations 18 Workshop for Small Animal Imaging 18 Example of Established Animal Models 19 Recent Important Publications 20

LOCATION 22 Scientifi c Environment & Culture 22 How to reach us 24 Contact Information 25

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contents

Page 4: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

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 PichlerChairPreclinical Imaging and Radiopharmacy

OUR MISSION

01

non-invasive small animal imaging – a new approach in biomedical research

02 | our mission

Page 5: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

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.

from mouse to man – from the laboratory bench to the patient’s bedside!

| 03

Page 6: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

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.

LABORATORY FOR PRECLINICAL IMAGING AND IMAGING TECHNOLOGY OF THE WERNER SIEMENS-FOUNDATION

02

preclinical imaging in tübingen

04 | laBoratorY

Page 7: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

development of funds and human resources

| 05

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.

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2005 2006 2007 2008 2009 2010

Funds raised in � (Million)*

*status June 2010

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201020092008200720062005

PhD studentsPostdocs

Technicians/EngineersAdministration

Personnel development

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2012012012012010000020020020020020099999200200200200200888882002002002002007777720020020020020066666200200000020 55555

PhD sPostdoc

Technicians/Administration

Page 8: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

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.

COOPERATIONS

03

cooperations with industry

06 | cooPerations

The Laboratory for Preclincal Imaging is hosted within the Department of Radiology of the University Hospital of Tübin-gen. This means:

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.

Currently our laboratory maintains collaborative research with more than six major national and international phar-maceutical companies.

Page 9: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

| 07

Institute of Medical Microbiology and Hygiene •(Prof. Autenrieth)

Department of Radiation Oncology (Prof. Bamberg)•

Department of Nuclear Medicine (Prof. Bares)•

Department of Diagnostic and Interventional Radiology •(Prof. Claussen)

Department of Diagnostic and Interventional •Neuroradiology (Prof. Ernemann)

Core Laboratory for Mouse Pathology (Prof. Fend)•

Department of Cardiology and Cardiovascular Medicine •(Prof. Gawaz)

University Children’s Hospital (Prof. Handgretinger)•

Department of General, Visceral and Transplant Surgery •(Prof. Königsrainer)

Department of Tropical Medicine (Prof. Kremsner)•

Department of Molecular Biology (Prof. Nordheim)•

Department of Immunology (Prof. Rammensee)•

Microarray Facility (Prof. Rieß)•

Department of Dermatology (Prof. Röcken) •

Interfaculty Institute for Biochemistry •(Prof. Feil, Prof. Schulze-Osthoff)

Department of Urology (Prof. Stenzl)•

Department of Toxicology (Prof. Schwarz)•

partners in tübingen

Max Planck Institute for Biological Cybernetics, •Tübingen, Germany

University of Münster, Germany•

University Hospital Heidelberg, Germany•

University of Freiburg, Germany•

Technische Universität München, Germany•

University of Erlangen-Nürnberg, Germany•

University of Mannheim, Germany•

University of Magdeburg, Germany•

Swiss Federal Institute of Technology Zurich, Switzerland•

Dr. Margarete Fischer-Bosch-Institut für Klinische •Pharmakologie (IKP), Stuttgart, Germany

Max Planck Institute for Physics, Munich, Germany•

University of California, Davis, USA•

Stanford University, California, USA•

Universität Innsbruck, Austria•

Paul Scherer Institute, Villigen, Switzerland•

Eindhoven University of Technology, Netherlands•

University of British Columbia, Canada•

external partners

academic cooperations

Page 10: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

INFRASTRUCTURE

04

08 | infrastructure

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.

imaging equipment

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•

Page 11: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

| 09

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 soft-ware 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.

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 per-sonnel, 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.

surgical interventions

Our animal imaging unit integrates a room for surgical in-terventions 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 sys-tem and warming pads to maintain and control the animals’ physiology during anesthesia.

Page 12: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

physiological monitoring

High quality and reliable animal imaging demands the well-being of the animals as well as a tight monitoring of physi-ological parameters and maintenance of body temperature. Our laboratory is therefore equipped with dedicated custom-made animal beds allowing the temperature monitoring as well as maintaining the body temperature of our animals. We apply monitoring equipment for ECG, respiration, sO2, blood pressure and blood gases.

translational imaging

The Laboratory for Preclinical Imaging and Imaging Technol-ogy not only focuses on small animal imaging, but also pro-vides infrastructure for large animal studies using our high resolution brain PET/MRI scanner (Siemens Healthcare, USA) as well as a clinical wholebody PET/CT scanner, 3 Tesla MRIs or latest clinical CT scanners. The laboratory within the De-partment of Radiology has full access to these tomographs. 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 stud-ies from mouse to man.

radiopharmacy unit

The affiliated Radiopharmacy unit (Chair: Prof. Pichler) pro-vides 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 pro-duction as well as for novel biomarker development. Beside the regular targets for 11C, 13N, 15O and 18F, our facility pro-vides 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

Page 13: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

in vivo meets in vitro

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

Blood gas analysis•

ELISA •

RT-PCR •

BLOT technology•

Autoradiography•

Gamma counting •

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-contamina-tion between cell lines.

our technological development pioneers molecular imaging

The laboratory not only performs innovative biomedical re-search but also pioneers the next generation of novel im-aging technology. Prof. Pichler’s group are leaders in the development of combined preclinical and clinical PET/MRI. Furthermore, our group is internationally recognized for achievements in developing novel detectors for next gen-eration PET scanners. We focus on compact semiconductor based sensors such as avalanche photodiodes (APDs) or Gei-ger mode APDs (G-APDs) connected to very fast, low noise electronic circuits.

| 11

Page 14: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

PROJECT EXAMPLES

05

12 | Project examPles

SCIENTIFIC AREAS

Neurooncology & Neurodegeneration•

Oncology•

Imaging in Immunology•

Morphological, Anatomical & •Functional Imaging

Imaging in Cardiology•

Infectious Diseases•

project management and study workflow

Project Idea Project Planning Ethical Approval

Pilot Study Data Analysis Data ReviewMeeting

• Allocation of Project Manager

• Cost Calculation

• Regular T-Cons • Personal Meeting

Data ReviewMeeting

Summarizing of Results

Planning of

Main Studies

Adapting Ethical Protocols

Main Study Data Analysis

• Regular T-Cons

• 1-2 Meetings

Phas

e 1

Phas

e 2

Phas

e 3

Phas

e 4

The chart below describes a typical study workfl ow contain-ing clearly predefi ned milestones which will be supported by project review meetings. An allocated project manager with experience in preclinical and translational research will be the responsible contact throughout the entire study. The project will be accompanied by regular teleconferences and exchange meetings to discuss results. This tight organisation ensures successful project workfl ows and identifi es problems at a very early stage.

Page 15: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

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PET/MR Oncology – Murine Astrocytoma Tumors

This project focuses on combined multimodality imaging of 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 para-meters such as membrane activity, proliferation and amino 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 of necrotic areas by use of diffusion weighted imaging and determination of tumor volume via anatomical MR imaging. The data obtained from PET and MRI are evaluated on an overall scale to gain insight into tumor metabolism. These in vivo imaging methods are complemented by ex vivo data such as histology.

neurooncology & neurodegeneration

The graph above shows the tumor volume of murine astro-cytomas as a function of time after implantation. The volu-me was determined using non-invasive MR imaging, thus allowing a clear determination of the tumor size at multiple time-points in the same animals.

Tum

or v

olum

e [m

m3 ]

Days after tumor implantation

Page 16: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

Parkinson’s disease is characterized by a progressive degener-ation of nigrostriatal dopaminergic neurons. PET has become a powerful tool for receptor and transporter quantification and has been used to study pathophysiology and disease progres-sion over time, as well as therapeutic effects in different animal models of neurodegenerative diseases. The reduction in striatal dopamine transporter binding, a measure of presynaptic dop-aminergic integrity, is established with [11C]methylphenidate, a radiotracer with a high affinity to the dopamine transporter. Changes in dopamine receptor density can be evaluated with [11C]raclopride, a radiotracer specific to D2-receptors and [11C]SCH-23390, a radiotracer specific to D1-receptors. For PET im-age quantification, regions of interest are drawn over an area

of interest in the brain and the activity over time is calculated. To determine receptor and transporter binding parameters, reference tissue models have become a valuable tool in brain studies of rats and mice without the need for an arterial input function from invasive arterial blood samples.

The binding potential (BPND) can be estimated from the Lo-gan graphical analysis using a linear regression equation of the target and the reference region. The distribution volume is calculated by the slope of the linear part of the plot and is equal to BPND+1.

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

14 | Project examPles

Page 17: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

oncology

| 15

Antibody Targeting of Prostate Cancer

Despite recent improvements in early detection and treatment, prostate cancer continues to be the most common malig-nancy 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 the 64Cu-labeled mAb in PSMA-positive tumors, these ligands represent excellent candidates for prostate cancer imaging agents and poten-tially for radioimmunotherapy.

Page 18: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

PET Biomarker Studies in Human Hormone-dependent Prostate Cancer Xenografted in Nude Rats

Clinical prostate cancer is a very heterogeneous disease; its behaviour ranges from indolent to aggressive states. Thus, imaging is challenging and the evaluation of new PET bio-markers is therefore important.

The clinical “gold standard” in oncology PET is [18F]FDG. How-ever for imaging prostate carcinoma (PCa) [18F]FDG is not suitable as high bladder activity makes it difficult to differ-entiate between prostate, malignant tissue and the benign prostatic hyperplasia or inflammation.

The PET tracers mainly used for clinical prostate PET imaging are currently [11C]Choline and its derivates. As metabolism 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).

The aim of this study is to validate [11C]Choline, [18F]FEC and [18F]FCh, three PET tracers specifically developed for pros-tate cancer imaging, and to compare them with [18F]FDG and [18F]FLT pre- and post-surgical castration in a hormone-dependent human prostate tumor model.

Tracer uptake is analyzed by acquiring time activity curves (TACs), standard uptake value (SUV) and tumour-to-muscle-ratio (T/M). In addition, we measured the apparent diffusion coefficient (ADC) and performed chemical shift imaging (CSI) of the xenogeneic nude rat model on a 7T MRI scanner. Imag-ing data are cross-correlated with molecular in vitro methods like immunohistochemistry and western blot.

The tumor-bearing nude rat is a useful in vivo model to study new PET tracers for human prostate cancer diagnostic and therapy efficacy monitoring.

Non-castrated Castrated

16 | Project examPles

Page 19: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

In vivo PET-Imaging of Inflammation and Hypoxia

Auto-antibodies against Glucose-6 phosphate isomerase (GPI) induce arthritis in mice that closely resembles human rheumatoid arthritis (RA). Angiogenesis and hypoxia play a major role in organ-specific autoimmune diseases such as GPI -arthritis. However, the exact mechanisms involved in neoan-giogenesis in RA remain enigmatic.

We use the GPI-arthritis model to evaluate hypoxia markers, gaining new insights into the molecular mechanisms which in-duce angiogenesis, hypoxia and eventually joint destruction.

We investigated the role of hypoxia-induced angiogenesis in GPI arthritis non-invasively in vivo using 18F-fluoroazomycin-arabinoside ([18F]FAZA) that selectively accumulates in hy-poxic tissue. Established ex vivo molecular biology methods, such as real time PCR, autoradiography, western blot and his-tology were also used to cross-correlate and validate the in vivo results.

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imaging in immunology

Page 20: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

The laboratory conducts collaborative research with ma-jor pharmaceutical companies in Germany, Europe and the world. We serve as the European Training and Reference La-boratory for Preclinical Imaging of Siemens HealthCare. Prof. Pichler is a board member of the Academy of Molecular Ima-ging (AMI), council member of the Society of Molecular Ima-ging (SMI) and the European Society for Molecular Imaging (ESMI), and heads the task force for preclinical molecular ima-ging at the German Association for Nuclear Medicine (DGN).

workshop for “small animal imaging”

The laboratory organizes and conducts an annual workshop for Small Animal Imaging, a successful event held for the fi fth time in a row in Tübingen in 2010.

The topics covered include:

Animal handling •

microPET •

microCT •

microSPECT •

7 T MRI •

Optical imaging •

High-resolution ultrasound•

Autoradiography, biodistribution, •cell labelling, microscopy

Image analysis •

REFERENCES

06

references and affiliations

18 | references

Page 21: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

Animal Models in OncologyProstate – Xenograft•

PC-3 (nu/nu mouse) –DU145 (nu/nu mouse) –CWR22 (nu/nu mouse) –

Melanoma•M21 –M21L –SKMEL28 –

Mamma – Endogenous•PyV-mT (C57BL/6) –PyV-mT (FVB) –

Colon •CT26 –

Pancreas – Endogenous (mouse)•RIP1-Tag2 (C3H) –

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

... and many more•

Animal Models in NeurologyAlpha-Synuclein (Parkinson, mouse)•3 different Alzheimer models •

Animal Models in ImmunologyGPI-Arthritis (mouse)•Contact allergy (TNCB, mouse)•Contact allergy (OVA, mouse)•

Experience in Imaging of other Animal Models in Cooperation with Companies

Colon – Xenograft: HCT116•Lung – Xenograft: H460•

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example of established animal models

Page 22: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

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

recent important publications

Page 23: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

M.S. Judenhofer, H.F. Wehrl, D.F. Newport, C. Catana, S.B. Sie-gel, M. Becker, A. Thielscher, M. Kneilling, M. Lichy, M. Eichner, K. Klingel, G. Reischl, S. Widmaier, M. Röcken, R.E. Nutt, H.-J. Machulla, K. Uludag, S.R. Cherry, C.D. Claussen, B.J. Pichler: Simultaneous PET/MRI: A new approach for functional and morphological imaging. Nat Med. 14(4):459-65, 2008

M. Kneilling*, L. Hültner*, B.J. Pichler*, R. Mailhammer, L. Mo-rawietz, S. Solomon, M. Eichner, J. Sabatino, T. Biedermann, V. Krenn, W. A. Weber, H. Ilges, R. Haubner, M. Röcken: Targeted mast cell cell–silencing prevents joint destruction and angio-genesis in experimental arthritis. Arth Rheum. 56(6):1806-1816, 2007 (*contributed equally)

B.J. Pichler, M. Kneilling, R. Haubner, H. Braumüller, M. Schwai-ger, M. Röcken, W.A. Weber: Imaging of delayed type hyper-sensitivity reaction by positron emission tomography and [18F]Galacto-RGD. J. Nucl. Med. 46(1):184-189, 2005

M. Kneilling, R. Mailhammer, L. Hültner, T. Schönberger, K. Fuchs, M. Schaller, D. Bukala, S. Massberg, C.A. Sander, M. Eich-ner, K.L. Maier, R. Hallmann, B.J. Pichler, R. Haubner, M. Gawaz, K. Pfeffer, T. Biedermann, M. Röcken: Direct Crosstalk between Mast Cell-TNF and TNFR1-expressing Endothelia Mediates Lo-cal Tissue Inflammation. Blood. 114(8):1696-706, 2009

U. Elsässer-Beile, G. Reischl. S. Wiehr, P. Bühler, P. Wolf, K. Alt, J. Shively, M.S. Judenhofer, H.J. Machulla, B.J. Pichler: PET ima-ging of prostate cancer xenografts with a highly specific anti-body against the postate specific membrane antigen. J Nucl Med. 50(4): 606-611, 2009

T. Wieder , H. Braumüller M. Kneilling, B. Pichler, M. Röcken: T cell-mediated help against tumors. Cell Cycle. 7(19):2974-7, 2008

N. Müller-Hermelink*, H. Braumüller*, B. Pichler*, T. Wieder, R. Mailhammer, K. Schaak, K. Ghoreschi, A. Yazdi, R. Haubner, C.A. 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)

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Page 24: Department of Radiology · University of Tübingen ...€¦ · Imaging Technology of the Werner Siemens-Foundation is to bridge the gap between in vitro biomedical research and in

Tübingen is a traditional, historic university town situated on the Neckar river, 40 km southwest of Stuttgart on the fringe of the Swabian Jura mountains and the Black Forest. The city fi rst appears in offi cial records in 1191, however the town’s fortress dates back to 1078. The Eberhard Karls University is one of Germany‘s oldest universities, internationally recog-nized for medicine, theological sciences and the humanities. It was founded in 1477 by Count Eberhard V.

The closest major city is Stuttgart, located 40 km northeastfrom Tübingen. Stuttgart, the capital of Baden-Württembergstate, provides all the shopping and cultural lifestyle of alarge city. It has a wide range of cultural offerings includingmuseums, 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 inter-national 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.

the Main research FocUs at the

FacUlty oF Medicine is cUrrently on

these areas:

Imaging and Medical Technology•

Infection Biology•

Oncology and Immunology•

Neuroscience•

Vascular Medicine and Diabetes•

LOCATION

07

scientific environment & culture

22 | location

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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 German Research Foundation (DFG), being one of the 20 Ex-cellence Clusters within Germany.

several close collaborations exist

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•

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Laboratory

24 | location

Due to the close proximity to Stuttgart, Tübingen is easilyreached by air. Stuttgart has a modern international airportwith non-stop fl ights to and from major international des-tinations.

You can reach Tübingen from the airport in about 20 min by car. Public transport by bus or train is also available.

By plane: The nearest international airport is Stuttgart (code: STR). From the airport, you can reach our lab within 20 min by car or taxi.

By train: You can reach our laboratory from Tübingen main station in 10 min by taxi or by bus line No. 5 in 7 min to the stop “Uni-Kliniken Tal”.

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

München

bahn A81 (Stuttgart-Singen) exit to Tübingen via “B28”.

Tübingen

Swabian Alb

Black Forest

Karlsruhe

SingenBodensee

Würzburg/Heilbronn

how to reach us

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Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-FoundationDepartment of Preclinical Imaging and RadiopharmacyEberhard Karls University TuebingenRoentgenweg 13, 72076 TuebingenGermany

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

Dr. Stefan WiehrProject manager for infectious diseases, oncologyPhone: +49-7071-29-83426 Email: [email protected]

Dr. Marcel KrügerProject manager for immunology, oncologyPhone: +49-7071-29-82972Email: [email protected]

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

Dr. Valerie HonndorfProject manager for oncologyPhone: +49-7071-29-87439Email: [email protected]

Dr. Carsten CalaminusProject manager for neurology, oncologyPhone: +49-7071-29-82972Email: [email protected]

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

Prof. Dr. Bernd Pichler ChairDepartment of Preclinical Imaging and RadiopharmacyPhone: +49-7071-29-83427 Email: [email protected]

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Eberhard Karls University Tuebingen

Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-FoundationDepartment of Preclinical Imaging and Radiopharmacy

Roentgenweg 13 · 72076 Tuebingen · Germanywww.preclinicalimaging.org


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