The research described in this proposal is the continuation of a program based on the premise that 99mTc will remain an important radionuclide in the practice of routine clinical nuclear medicine. The primary thrust is the development of new agents in two areas, coupled with some carefully selected chemical studies intended to add flexibility in the design of the product complexes and, thus, their biologic behavior. The first major aim is to continue the evaluation of technetium complexes capable of detecting the presence of malignant melanoma in vivo. Over this current cycle, several potential candidates have been identified as showing significant uptake in animal models of melanoma, including one of metastatic spread to the lungs. A new high resolution microSPECT camera has now made possible longitudinal studies that allow monitoring of tumor growth with time, a highly useful capability that will be pursued further in the proposed period. The second major aim is to continue designing complexes that have affinity for the 5HT1A receptor. Over the past few years it has become increasingly clear that, apart from their established function in the central nervous system, neurotransmitter systems play a significant role in the growth and spread of cancer throughout the human body. Thus, it is planned to assay uptake in both normal brain and in vivo models of prostate cancer, an example of tumors that express this receptor type. The search for complexes with high affinity and selectivity for 5HT1A receptors increases in importance with the prospect of important dual purposes for the research. The third major aim is to examine the chemical behavior and ligand preferences of two metal cores as alternatives to the Tc/Re(V) oxo core used in aims 1 and 2: the relatively well-studied Tc(l) tricarbonyl core and the less well-explored Tc(l) nitrosyl core. This chemistry will be conducted in support of the work in aims 1 and 2 in that the latter cores should provide more flexibility in the design of the final platform for mounting a given biologically active moiety. Malignant melanoma and prostate cancer are both serious public health problems in this country. This work is designed to develop a means of detecting these tumors in the clinic using noninvasive imaging techniques. The microSPECT imaging capability with small-animal models could also prove useful in preclinical studies assessing the development of new therapies for these diseases. ? ?
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