SANDOSTATIN(R) LABELED WITH TC-99M - IN-VITRO STABILITY, IN-VIVO VALIDITY AND COMPARISON WITH IN-111-DTPA-OCTREOTIDE

Sandostatin(R), a synthetic octapeptide analog of a native hormone som atostatin, was labeled with a commonly available, inexpensive radionuc lide, Tc-99m, and evaluated for its suitability for in vivo imaging. L abeling was accomplished by reduction of the cystine bridge, which pro vided two sulfhydryl groups for chelation with Tc-99m. The complex was examined for thermodynamic stability in vitro and in experimental ani mals. Receptor specificity of the complex was determined using rat bra in cortex membrane rich in somatostatin receptors, and its tissue dist ribution was studied in nude mice bearing human prostate cancer In the se studies, Tc-99m-labeled oxytocin, a nonspecific peptide with simila r molecular weight, sewed as a control and In-111-DTPA-octreotide sewe d as a standard The labeling method was simple, did not require protec ting and deprotecting functional groups and yields were high (ca. 70%) . The in vitro and in vivo stability was excellent, and K-d values wer e in the nanomolar d range, similar to those of In-111-DTPA-octreotide . At 24 hours post-injection, the tumor uptake for Tc-99m-Sandostatin, expressed as percent of injected dose per gram (% ID/g), was higher b ut the tumor/blood and tumor/muscle ratios were lower than those for I n-111-DTPA-octreotide. This agent, with its improved target-to-nontarg et ratios, should prove to be of value for imaging somatostatin recept or-positive tumors.