Vapreotide labeled with Tc-99m for imaging tumors

Abstract

Vapreotide (RC-160), an octapeptide analog of somatostatin, has a high affinity for somatostatin receptor subtypes SSTR2 and SSTR5. Vapreotide binds differently to the tumors of the breast, ovary, exocrine pancreas, prostate and colon, than octreotide another octapeptide analog of somatostatin. Vapreotide was labeled with Tc-99m, a radionuclide highly suitable for scintigraphic imaging. The labeling procedure was simple, produced >70% yields and could be applicable to label other peptides containing a cystine bridge. HPLC analysis showed that the tracer was stable when Tc-99m-RC-160 was challenged with 100 fold molar excess DTPA (diethylenetriaminepentaacetic acid), HSA (human serum albumin) or cysteine and incubated at 37 degrees C for 4 h. HPLC analysis of urine samples obtained from mice that received Tc-99m-RC-160 showed that the preparation was stable in vivo. Rat brain cortex membrane receptor displacement assays showed that the Kd values for Tc-99m-RC-160 (71x10(-9) M) and Tc-99m-octreotide (86x10(-9) M) (Sandostatin(R)) were in nM range, and were similar to that for I-125-RC-160 (46x10(-9) M). High binding affinity of Tc-99m-RC-160 for human breast tumor cells SKBR-3 was also observed. These results suggest that Tc-99m-RC-160 is worthy of evaluation as an agent for scintigraphic imaging of tumors rich in somatostatin receptor subtypes SSTR2 and SSTR5.