TECHNETIUM-RADIOLABELED SOMATOSTATIN RECEPTOR BINDING PEPTIDES FOR IMAGING CERTAIN CANCERS

CANCER IS THE SECOND LEADING CAUSE OF DEATH IN THE U.S. IN MANY CASES, EARLY AND COMPLETE DETECTION IS CRUCIAL TO A POSTIVE PROGNOSIS. THIS OFTEN REQUIRES DETECTION AT A STAGE WHEN A TUMOR IS TOO SMALL OR TOO POORLY DIFFERENTIATED FROM NORMAL TISSUE TO BE DETECTED BY CONVENTIONAL ANATOMIC IMAGING. CELL SURFACE RECEPTORS FOR THE GROWTH HORMONE RELEASE-INHIBITOR SOMATOSTATIN (SRIF) ARE HYPER-EXPRESSED BY A NUMBER OF CANCERS. (123)I-[TYROSINE(3)]-OCTREOTIDE AND (111)IN-[DTPA] (DIETHYLENETRIAMINEPENTAACETIC) OCTREOTIDE ARE RADIOLABELED SMALL PEPTIDE ANALOGUES OF SRIF THAT BIND WITH HIGH AFFINITY TO SRIF RECEPTORS AND HAVE BEEN SHOWN TO BE EXTREMELY USEFUL IN DETECTING CERTAIN CANCERS INCLUDING SMALL CELL LUNG CARCINOMA, PANCREATIC CARCINOMA, LYMPHOMA, AND SOME BREAST CANCERS. HOWEVER TECHNETIUM ((99M)TC) IS THE PREFERRED NUCLEAR MEDICINE ISOTOPE BECAUSE IT YIELDS GREATER PHOTON FLUX PER UNIT OF RADIATION DOSE DELIVERED TO THE PATIENT, HAS A CONVENIENT 6 HOUR HALF-LIFE, IS RELATIVELY INEXPENSIVE, AND IS AVAILABLE 24 HOURS A DAY FROM AN IN-HOUSE GENERATOR. THEREFORE A (99M)TC-LABELED SMALL, SYNTHETIC SOMATOSTATIN-RECEPTOR BINDING PEPTIDE SHOULD COMBINE THE DOCUMENTED DIAGNOSTIC EFFICACY OF THE (123)I AND (111)IN AGENTS WITH THE SIGNIFICANT ADVANTAGES OF (99M)TC AS THE RADIONUCLIDE. THE GOAL OF THIS PROJECT IS TO DEVELOP A NUCLEAR MEDICINE IMAGING AGENT THAT IS A (99M)TC-LABELED SMALL, SYNTHETIC SRIF-RECEPTOR BINDING PEPTIDE FOR IMAGING SRIF-RECEPTOR EXPRESSING TUMORS. TO MEET THESE OBJECTIVES, IT IS PLANNED TO PREPARE AND ASSAY INVITRO APPROXIMATELY 20 PEPTIDE-CHELATOR CONJUGATES AND THEIR RHENIUM COMPLEXES. FURTHERMORE, (99M)TC COMPLEXES WILL ALSO BE PREPARED AND TESTED IN ANIMALS BEARING SSTR-EXPRESSING TUMORS.