title: Novel somatostatin analogs for the treatment of acromegaly and cancer exhibit improved in vivo stability and distribution.
abstract: The biodistribution of several radiolabeled somatostatin (SRIF) analogs was determined in the rat. Newly developed analogs BIM-23190 and BIM-23197 attained higher plasma levels and much greater target tissue concentrations than the clinically used BIM-23014 analog. Highest tissue concentrations of BIM-23190 and BIM-23197 were found in adrenal, kidney, pituitary and pancreas, tissues that are known to be abundant in mRNA for the somatostatin subtype 2 receptor. BIM-23190 and BIM-23197 associated radioactivity in these tissues was prolonged compared with that 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 elevated plasma and target tissue concentrations of these new SRIF analogs. Based on higher plasma levels, greater distribution to target tissues 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 types of cancer.
authors.affiliation: Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Gillespie
authors.forename: A
authors.initials: A
authors.lastname: Erenberg
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Dong
authors.forename: J E
authors.initials: JE
authors.lastname: Taylor
authors.forename: V
authors.initials: V
authors.lastname: Hau
authors.forename: T P
authors.initials: TP
authors.lastname: Davis
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical; D008297:Male; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics*; D010456:Peptides, Cyclic / Q000097:blood / Q000493:pharmacokinetics*; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; C111783:BIM 23190; C111784:BIM 23197; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010879:Piperazines; C060347:lanreotide; D013004:Somatostatin