Experimental Projects

a) Labeling of tumor-specific antibodies for diagnostics and therapy.

The evaluation of the new tracers takes place in animal experiments and in clinical trials. Currently, lymphomas are enrolled as as target tumors. An EGF receptor antibody for the treatment of ENT tumors is found in animal experiments.

b) Development of tumor models with expression of genes for antiangiogenesis

This allows the measurement of the functional consequences of antiangiogenic strategies by means of positron emission tomography (PET) as well as the comparison of these nuclear medicine data with histological (immunohistology) and molecular biology (expression pattern) data. The project is carried out in close cooperation with PD Dr. Ralf Kinscherf (Department of Anatomy and Cell Biology III, University of Heidelberg). The functional consequences, such as the effect on perfusion, proliferation or apoptosis, but also the defense mechanisms of the tumor, can be further characterized in these models.

c) Development of new therapies for non-iodine-storing thyroid carcinomas

Redifferentiation therapies with retinoic acid and ligands for the peroxisome proliferator-activated receptor g '(PPARg) are currently being used.

d) Identification of tumor-affine molecules

This method uses mainly phage display techniques to achieve targeting of peptides against prostate and thyroid carcinomas. The information obtained in these studies is used for the optimization of the peptides for the diagnosis of tumors as well as for therapeutic purposes by coupling the peptides to potential therapeutics. Both chemotherapeutic agents and radioactive isotopes are suitable as coupling partners. In addition, radioactive-labeled antibodies are evaluated in pre-clinical and clinical trials for the treatment of lymphoma as well as for solid tumors.

e) Detection of gene transfer or its effects on the tumor

Suicide genes such as the HSV thymidine kinase or the cytosine deaminase are used here. In addition, genes are used, which are supposed to lead to the accumulation of radioactive isotopes. On the one hand, this strategy is based on the concept of radioiodine therapy and attempts to achieve storage of 131I in the tumors by the transfer of the genes for the sodium iodide symporter or peroxidases. On the other hand, it is attempted to achieve an accumulation of 131I-MIBG by the transfer of the norepinephrine transporter gene. First results show that the transfer of these genes does not lead to therapeutically useful doses per se, but that the sodium iodide symporter can be used as an in vivo reporter gene for non-invasive presentation of gene transfer or promoter activation. The transfer of genes for thyroid transcription factors such as TTF1 and pax-8 or the gene for PPARg can be used to represent functional protein-protein interactions. Furthermore, the effects of these factors on the redifferentiation of tumors are investigated. In parallel, in cooperation with the Department of Endocrinology of the University, a clinical study on the redifferentiation of non-iodine-storing thyroid carcinomas takes place. Furthermore, the generation of tumor lines with the expression of caspases or receptors can be used to evaluate new tracers for the presentation of apoptosis or the receptor expression of tumors.

f) Construction of tissue- or tumor-specific viral vectors

As a tumor-specific system, promoters and enhancers of thyroid-specific genes such as sodium iodide symporter, peroxidase and thyroglobulin, as well as the promoter / enhancer for glucose transporter type 1 (GLUT1) are used in this method. GLUT1 is overexpressed in most tumors and also very early after malignant transformation of benign cells.

g) Preclinical studies of the pharmacokinetics of high molecular weight drugs

With the modern methods of drug development, in particular high-throughput screening methods, new drugs can be identified very efficiently for their binding to specific targets. Following the identification of the large number of lead structures, which are characterized exclusively in vitro, there is a need for industrial partners to carry out the subsequent investigation in vivo using efficient methods. Nuclear medical procedures enable rapid pharmacokinetic parameters to be obtained. In particular, high-molecular substances, such as viral proteins or antibodies, can be radioactively labeled and examined in the animal model efficiently and with a minimal influence on the biological activity.

h) Animal studies in a rat fracture model with induced osteoporosis using dPET-CT using FDG and F-18 fluoride.

Here, the effect of osteoporosis on tracer kinetics as well as the change in tracer kinetics during defect healing will be investigated. Furthermore, the influence of different bone replacement materials on the healing should be assessed.

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