Synthesis Of Radionuclide Imaging Agents For Detecting Tumor Receptors

Radioactive somatostatin analogs and other receptor-positive imaging agents are the newest and most attractive radiopharmaceuticals which have aroused wide interest of nuclear medicine scientists and physicians throughout the world. Among them, the most well-known one is the radioactive octreotide which is now available solely from a pharmaceutical company in Netherlands.To study the synthesis of these active peptide is a prerequisite to use these valuable radiopharmaceuticals in our country and catch up the most recent advance in modern nuclear medicine.Our study consists of the chemical synthesis of biologically active peptides, labeling of these peptide with I-131, culture of pancreatic cancer and breast cancer cells, use of tumor-bearing nude mice as animal models, biodistribution of I-131-peptides and imaging of tumors with these peptides in nude mice.Part 1. I-131-Tyr-3-Octreotide:a radioiodinated somatostatin analog which binds to somatostatin receptor-positive tumorsOctreotide is a highly active, long-acting somatostatin analog, which has a high affinity to somatostatin receptors. In our attempt to synthesize this peptide, three methods were explored. The first two methods were unsuccessful, but they afforded us useful experience which we could use with profit to make a new design. A satisfactory synthetic product was finally obtained by means of the third method.(1) The first method: We chose the BOC strategy for the solid phase peptide synthesis (SPPS). The cysteine was blocked with MeBzl, Tyr with BrZ, D-Trp with CHO, Lys with C1Z, and Thr with Bzl, respectively. At the early period we used TFMSA/TFA to cleave the peptide-resin and remove the side chain protective groups. Thioanisole or phenol was used to entrap side chain protective groups. After many trials, we found that TFMSA was unable to remove some side chain group, such as MeBzl, and the peptides in TFMSA were more...