The formation of cancer is normally accompanied by changes in metabolic features of neoplastic tissue when compared with normal tissue. During the last few years we capitalized in this conceptand developed the necessay expertise to synthesize and test a group of metabolic tracers, amino acids, sugars and their analogs as specific agents for visualization of tumors. Our results with positron labeled sugars and (N-13) amino acids indicate that this approach is useful. The main objective of this research proposal is to continue the development of radiopharmacueticals bearing positron radionuclides for imaging and quantitation of organs containing neoplastic diseases. The emphasis, however, will be on agents with known specific metabolic agents processes. The behavior of these radiolabeled specific agents will be evaluated in tumor tissues for their rate of tissue uptake and clearance to determine the functional status and morphology of neoplastic tissue prior to, during and after radiotherapy treatment. The radiopharmaceuticals of choice are D and L (F-18)fluoro amino acids of methionine and leucine and their D and L Alpha-methyl derivatives. The transport and incorporation of these new amino acids into proteins will be studied in the animal tumor model. (F-18)DOPA will be prepared to study the selective incorporation of this melanin precursor into melanotic cells and melanoma deposits. Diadenosine 5',5'''-p1,p4-tetraphoshate was found to be incorporated into well identified human malignant cells. Its (C-11) label will be prepared and studied in specific cell cultures and tumor cells.
