title: Radiotherapeutic efficacy of (153)Sm-CMDTPA-Tyr(3)-octreotate in tumor-bearing rats.
abstract: A number of radiolabeled somatostatin analogs have been evaluated in animal tumor models for radiotherapeutic efficacy. The majority of the agents tested have used either high-energy beta-emitters, such as Y-90 or Re-188, or the Auger electron-emitting radionuclide, In-111. Because a medium-energy beta-emitter might have equivalent efficacy compared to high-energy emitters, and lower toxicity to non-target tissues, we have evaluated the therapeutic potential of the beta-emitting nuclide, Sm-153, chelated to the somatostatin analog, CMDTPA-Tyr(3)-octreotate. Using an in vitro binding assay, this octreotate derivative was shown to have high affinity for the somatostatin subtype-2 receptor (IC(50) = 2.7 nM). Biodistribution studies in CA20948 tumor-bearing Lewis rats demonstrate that the Sm-153 labeled compound has high uptake and retention in tumor tissue (1.7% injected dose/g tissue, 4 hrs post injection) and has rapid overall clearance properties from non-target tissue. Radiotherapy studies were carried out using (153)Sm-CMDTPA-Tyr(3)-octreotate and CA20948 tumor bearing Lewis rats at 7 days post implant. Dose regimens consisting of single and multiple i.v. injections of 5.0 mCi/rat (185 MBq) were employed over a time span of 7 days. Suppression of tumor growth rate was observed in all treated animals compared to untreated controls. Greater inhibition of tumor growth was observed in animals that received multiple doses. These studies indicate that medium-energy beta-emitting isotopes have considerable potential for the treatment of somatostatin receptor-positive tumors.
authors.affiliation: Mallinckrodt Inc., Department of Discovery Research, PO Box 5840, St. Louis, Missouri 63134, USA. jebugaj@mkg.com
authors.forename: J E
authors.initials: JE
authors.lastname: Bugaj
authors.forename: J L
authors.initials: JL
authors.lastname: Erion
authors.forename: M A
authors.initials: MA
authors.lastname: Johnson
authors.forename: M A
authors.initials: MA
authors.lastname: Schmidt
authors.forename: A
authors.initials: A
authors.lastname: Srinivasan
mesh_terms: D000818:Animals; D005998:Glycine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: C433517:CMDTPA-Tyr(3)-octreotate; D019275:Radiopharmaceuticals; D013004:Somatostatin; D005998:Glycine