Synthesis, radiolabeling and biological evaluation of a neutral tripeptide and its derivatives for potential nuclear medicine applications

Peptides are important regulators of growth and cellular functions not only in normal tissue but also in tumors. So they are becoming radioligands of increasing interest in nuclear oncology for targeted tumor diagnosis and therapy. So development of new peptide radiopharmaceuticals is becoming one of the most important areas in nuclear medicine research. A small tripeptide derivative NH2PhePheCys was synthesized by Fmoc solid phase peptide synthesis using an automated synthesizer. The oxidized form, i.e. NH2PhePheCysCysPhePheNH2, was also prepared by iodine oxidation method from NH2PhePheCys(ACM). The ligands were analyzed by HPLC and mass spectroscopy. They were radiolabeled with 99mTc using SnCl2. In vitro analytical studies and biological characterizations were performed using the peptide radiopharmaceuticals. Images taken under gamma camera showed very high uptake in the liver, lung and spleen. Significant uptake was also observed in bone marrow and brain for 99mTc-NH2PhePheCys. Metabolites were produced in vivo when the radiopharmaceuticals were injected intravenously and were identified from rat brain and liver homogenate studies. Clearance through kidney did not show any evidence of breaking of the labeled compounds and formation of free 99mTc. Radiopharmaceuticals prepared using tripeptide and hexapeptide ligands were transported into the brain through blood brain barrier depending on the size and sequence characteristics. Using this property of peptide new derivatives can be prepared to develop 99mTc radiopharmaceuticals for imaging normal brain tissues as well as for diagnosing various brain disorders.