NOVEL SOMATOSTATIN ANALOGS FOR THE TREATMENT OF ACROMEGALY AND CANCEREXHIBIT IMPROVED IN-VIVO STABILITY AND DISTRIBUTION

The biodistribution of several radiolabeled somatostatin (SRIF) analog s was determined in the rat. Newly developed analogs BIM-23190 and BIM -23197 attained higher plasma levels and much greater target tissue co ncentrations than the clinically used BIM-23014 analog. Highest tissue concentrations of BIM-23190 and BIM-23197 were found in adrenal, kidn ey, pituitary and pancreas, tissues that are known to be abundant in m RNA for the somatostatin subtype 2 receptor. BIM-23190 and BIM-23197 a ssociated radioactivity in these tissues was prolonged compared with t hat of BIM-23014, especially in the SRIF-receptor-rich pituitary. BIM- 23190 and BIM-23197 were more stable in vivo and much less subject to biliary excretion than BIM-23014. These properties account for the ele vated plasma and target tissue concentrations of these new SRIF analog s. Based on higher plasma levels, greater distribution to target tissu es and longer in vivo stability, BIM-23190 and BIM-23197 may prove to be superior to BIM-23014 for the treatment of acromegaly and some type s of cancer.