Department of Radiopharmaceutical and Chemical Biology
Our efforts focus on biochemistry, biology, imaging, and therapy of malignant solid tumors and metastases, with emphasis placed on melanoma, pheochromocytoma, pancreatic ductal adenocarcinoma and multiple myeloma. The discovery and functional characterization of tumor-specific membrane and intracellular proteins, and subset parameters of tumor microenvironment in vitro and in vivo are objectives of several projects and collaborations. This topic implicates pre-clinical research intended to evaluate the theragnostic potential of recent discoveries in the basic mechanisms of both solid tumor pathogenesis and metastasis. Therefore, our research encompasses a broad spectrum of laboratory activities, directed on pharmacological characterization of novel radiolabeled and non-radioactive compounds for either diagnostic or therapeutic use in cell, organ and animal models to determine a) biodistribution, kinetics, and metabolism of novel radiotracers, b) pharmacodynamics of cognate candidate compounds for targeted radionuclide therapy, and c) therapeutic potential of natural and synthetic compounds for application as adjuvant targeted radioprotective or radiosensitizing agents. The resulting data including information obtained by multimodal small animal imaging techniques are used in elucidation of structure-activity relationships as well as providing a basis for assessing potential clinical utility. The best compounds identified in initial screening are subsequently examined in more sophisticated models that allow, under a variety of physiological conditions, direct evaluation of the relationship between compound action and specific aspects of both tissue pathobiochemistry and pathophysiology. For promising compounds identified in this manner, we have productive collaborative relationships with a number of investigators that allow for additional preclinical and clinical assessment of theragnostic performance. Our strategic goal is to contribute to the elucidation of mechanisms of tumor therapy resistance, especially in endoradiotherapy. Special interes is given to mechanisms characterized by the involvement of extracellular matrix and matrix-modifying proteins. Innovative therapeutic approaches will be identified.