Intern
Krebsforschung

Preclinical Molecular Imaging

Molecular imaging with positron emission tomography (PET) allows sensitive detection and functional characterization of cancer deposits in the entire body. Because of heterogeneous response rates, molecular imaging has been suggested to identify response very early in the course of therapy. Imaging is also important for drug development by identification of the most effective compound and by elucidating specific mechanisms of action. Relevant targets for imaging include the process of neoangiogenesis, altered membrane protein expression, cell adhesion, cell migration, microenvironment and DNA replication. The development and validation of innovative imaging probes which are capable of addressing biological targets associated with the therapeutic effect will be a major contribution to the CCC.

The Dept. of Nuclear Medicine is located at the Centre for Internal Medicine (ZIM) and provides excellent facilities for molecular imaging in the preclinical and clinical setting, including a state-of-the-art Cyclotron (GE PET Trace 6) and a GMP-certified laboratory for the production of biomarkers for cancer imaging. At the nearby Centre for Experimental Medicine (ZEMM), all tools necessary for tracer development and preclinical evaluation are available (radiochemistry, cell culture, animal models, small animal PET (Siemens Inveon), and microCT). In cooperation with the Bio Imaging Centre (BIC) at the Rudolph Virchow Centre and the Dept. of Experimental Physics, optical imaging techniques and small animal MRI (17.6T) are available to the members of the CCC.

Multiparametric small animal imaging can be offered, including structural imaging (CT, US), physiologic (MRI) and molecular or metabolic imaging (PET). Available biomarkers for functional imaging are listed in table 1. Imaging can be performed at various time points to study drug effects.
Funding

The service unit is funded by the Medical Faculty of the University of Würzburg (IZKF), the Chronic Heart Failure Centre Würzburg and the Dept. of Nuclear Medicine. A low fee accounting for maintenance and disposables will be charged for imaging studies.

Research covers targeted and functional imaging for staging and target definition, radiotherapy planning, multi-modality treatment planning including individual dosimetry, high-accuracy treatment delivery, response monitoring and treatment adaptation. These technologies have already been successfully transferred into prospective clinical trials and patient treatment with a special focus on lung and prostate cancer. The Depts. of Nuclear Medicine and Internal Medicine I have developed specific radiopharmaceuticals to diagnose and treat adrenal tumors by targeting specific enzymes. In collaboration with the Dept. of Radiooncology, a similar program has been established for specific targeting of gliomas via amino acid transporters and for castration-resistant prostate cancer.

Imaging Biomarkers available to Members of CCC MF

surrogate marker compound pathophysiologic correlate
[18F]FDG 2`-[18F]fluoro-2`-Deoxyglucose glucose metabolism
[18F]FLT 3`-[18F]fluoro-3`-Deoxythymidine DNA synthesis
[68Ga]DOTA-TOC [68Ga]-DOTA-DPhe1-Tyr3-octreotide expression of somatostatin receptors (SSTR 2)
[11C]choline [11C]choline lipid metabolism
[11C]methionine [11C]methionine protein biosynthesis
[18F]fluoroethyltyrosine [18F]fluoroethyltyrosine amino acid transport
[18F]galacto-RGD/ [68Ga]NOTA-RGD avβ3 integrin receptor ligand angioneogenesis
[18F]fluoride [18F]fluoride bone seeking agent
[18F]-AZA [18F]fluoromisonidazole hypoxia specific agent
[18F]rituximab [18F]labelled anti-CD20 monoclonal antibody anti-CD 20 antibody
[123I]IPA [123I]iodophenylalanine amino acid transport
[123I]IMTA [123I]iodometomidate adrenal CYP11B enzymes