Many peptides are involved in biological systems as biochemical and physiological modulators or chemical messengers. A number of tumors also possess high affinity receptor sites for specific peptides. To date, constraints in chemistry have limited the utilization of important biologically active peptides as in vivo tracers in nuclear medicine. This study involves the developmental chemistry to allow the incorporation of technetium-99m, the ideal radionuclide for both planar and single photon emission computed tomography (SPECT), into bioactive peptides. The utilization of donor atoms from small peptides for the coordination of technetium may inactivate the peptide. Therefore, the diaminedithiol ligand system which has been proven to readily form extremely stable complexes with technetium will be used as a carrier of the radiometal. Convenient diaminedithiol bifunctional synthetic intermediates will be developed for one or two step synthesis of coupled evaluation. The coupling of the diaminedithiol ligand system to the peptide will be accomplished through terminal amino and carboxylic groups, side chain functional groups such as the e-amino group of lysine, the guanido group of arginine, the group of glutamate or aspartate. The utility of the chemical methods to be developed will be evaluated using two classes of bioactive peptides, namely, chemotactic peptides and analogs of neutrophils and macrophages. The methods will be useful for imaging focal sites of inflammation or infection. The neurotensin analogs will be useful for studies in cancer (such as neuroblastoma, colon and small cell cancer of the lungs), schizophrenia and the mechanism of action of neuroleptic drugs.
Showing the most recent 10 out of 88 publications
