title: [177Lu-DOTA(0),Tyr3] octreotate for somatostatin receptor-targeted radionuclide therapy.
abstract: Receptor-targeted scintigraphy using radiolabeled somatostatin analogs such as octreotate is being used with great success to demonstrate the in vivo presence of somatostatin receptors on various tumors. A new and promising application for these analogs is radionuclide therapy. Radionuclides suitable for this application include the Auger electron-emitter (111)In and the beta-emitters (90)Y (high energy) and (177)Lu (low energy). We investigated [DOTA(0),Tyr(3)]octreotate, labeled with the lanthanide (177)Lu, in biodistribution and radionuclide therapy experiments using male Lewis rats bearing the somatostatin receptor-positive rat CA20948 pancreatic tumor. Biodistribution studies in Lewis rats showed the highest uptake in the rat pancreatic CA20948 tumor and sst(2)-positive organs, which include the adrenals, pituitary and pancreas, of [(177)Lu-DOTA(0),Tyr(3)]octreotate in comparison with (88)Y- and (111)In-labeled analogs. Kidney uptake of [(177)Lu-DOTA(0),Tyr(3)]octreotate could be reduced by approximately 40% by co-injection of 400 mg/kg D-lysine. In radionuclide therapy studies, a 100% cure rate was achieved in the groups of rats bearing small (< or =1 cm(2)) CA20948 tumors after 2 doses of 277.5 MBq or after a single dose of 555 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate. A cure rate of 75% was achieved after a single administration of 277.5 MBq. In rats bearing larger (> or =1 cm(2)) tumors, 40% and 50% cure rates were achieved in the groups that received 1 or 2 277.5 MBq injections of [(177)Lu-DOTA(0),Tyr(3)]octreotate, respectively. After therapy with [(177)Lu-DOTA(0),Tyr(3)]octreotide in rats bearing small tumors, these data were 40% cure after 1 injection with 277.5 MBq and 60% cure after 2 repeated injections. In conclusion, [(177)Lu-DOTA(0),Tyr(3)]octreotate has demonstrated excellent results in radionuclide therapy studies in rats, especially in animals bearing smaller tumors. This candidate molecule shows great promise for radionuclide therapy in patients with sst(2)-expressing tumors.
authors.affiliation: Department of Nuclear Medicine, University Hospital and Erasmus University Rotterdam, 3015 GD Rotterdam, The Netherlands. dejong@nuge.azr.nl
authors.forename: M
authors.initials: M
authors.lastname: de Jong
authors.forename: W A
authors.initials: WA
authors.lastname: Breeman
authors.forename: B F
authors.initials: BF
authors.lastname: Bernard
authors.forename: W H
authors.initials: WH
authors.lastname: Bakker
authors.forename: M
authors.initials: M
authors.lastname: Schaar
authors.forename: A
authors.initials: A
authors.lastname: van Gameren
authors.forename: J E
authors.initials: JE
authors.lastname: Bugaj
authors.forename: J
authors.initials: J
authors.lastname: Erion
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: A
authors.initials: A
authors.lastname: Srinivasan
authors.forename: E P
authors.initials: EP
authors.lastname: Krenning
mesh_terms: D000818:Animals; D001345:Autoradiography; D002614:Chelating Agents / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism; D008187:Lutetium / Q000627:therapeutic use*; D008297:Male; D015282:Octreotide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy*; D011868:Radioisotopes / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D051381:Rats; D011917:Rats, Inbred Lew; D017481:Receptors, Somatostatin / Q000032:analysis*; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D011868:Radioisotopes; D017481:Receptors, Somatostatin; C045210:3-Tyr-octreotide; D008187:Lutetium; D015282:Octreotide