Several
somatostatin analogs with recently synthesized acetylated N terminus were assayed in vivo for their effects on
sodium pentobarbital-stimulated
growth hormone (GH) levels in fed male rats and
gastrin-releasing peptide (14-27)-stimulated
gastrin levels in fasted male rats. The binding characteristics of these analogs to
somatostatin receptors were also examined in various human
tumors and normal tissues. The analog RC-101-I, injected at a dose of 0.1 micrograms/100 g body wt, significantly suppressed GH release (P less than 0.01) for at least 2 hr. Analog RC-160-II caused the longest inhibition of GH release, greater than that induced by nonacetylated parent analog
RC-160, with GH levels showing significant suppression (P less than 0.01) for more than 3 hr. Analogs RC-160-II and RC-101-I and
RC-160, injected at a dose of 1.0 micrograms/100 g body wt, significantly (P less than 0.01) suppressed
gastrin-releasing peptide (14-27)-stimulated serum
gastrin. Analog RC-101-I was active in this test at a dose of 0.1 micrograms/100 g body wt. RC-160-II showed significant binding to
somatostatin-14 receptors in all investigated tissues (human colon, human
colon cancer,
breast cancer, human pancreas and
pancreatic cancer, human prostate and
prostate cancer, and rat cerebral cortex), but there were marked variations in binding affinities among various normal and cancerous tissues. The highest affinity was found in membranes of
colon cancer (Ka = 18.4 nM-1) and
breast cancer (Ka = 12.46 nM-1). The binding affinity of RC-160-II to
somatostatin receptors in membranes of the
breast cancer was similar to that of
RC-160. RC-101-I showed higher binding affinity to
somatostatin-14 receptors than
RC-160 in human breast, pancreatic, and
prostate cancer. With the exception of
breast cancer tissue, the binding affinity of RC-101-I was significantly lower than that of RC-160-II in membranes of all investigated tissues. It can be concluded that acetylated
somatostatin analogs RC-101-I and RC-160-II possess prolonged and enhanced
biological activities in suppressing serum GH and
gastrin in rats. Significant variations in binding affinities for these analogs in different tissues and various
tumors suggest that differences may exist between
somatostatin receptors in normal versus malignant tissues. This raises the possibility that some of these analogs could be used more selectively in the treatment of various
neoplasms.