The purpose of this project is to utilize the previously developed F-18 labeling agent, N-succinimidyl 4-[18F](fluoromethyl)benzoate, to labeled various target molecules for tumor detection. The advantage of using this radiolabeling agent is that this agent can be made in one chemical step with a short synthesis time. The labeling procedure can be automated when large amount of activity is required. An improved method for preparation of N-succinimidyl 4-[18F](fluoromethyl) benzoate has also been developed with a 50% increase of radiochemical yield by using a better leaving group. The new ligand is a nitro substituted analog of previously developed N-succinimidyl-4[(4- nitrobenzene-sulfonyl)oxymethyl)benzoate. Transferrin, somatostatin, anti-tac disulfide stabilized monoclonal antibody variable-region fragments, and vasoactive intestinal peptide have been labeled with N-succinimidyl 4-[18F]-(fluromethyl)benzoate. In vivo and in vitro biological tests also have been performed with these labeled molecules. Biodistribution studies were performed for all above labeled compound using normal and tumor bearing mice. Radiolabeled transferrin and anti-tac disulfide stabilized monoclonal antibody variable-region fragments were used to image the tumor mice. Positive results were obtained for, both biodistribution study and image study. In vivo metabolism study was performed with radiolabeled anti-tac disulfide stabilized monoclonal antibody variable-region fragments in order to better understand the activity uptake by different organs. Both mice and baboon were used in metabolism study. Possible radioactive metabolites were also synthesized. The major metabolites were found to be the F-18 labeled lysine and N-a-acetyl lysine.
