[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: M de Jong, W A Breeman, B F Bernard, W H Bakker, M Schaar, A van Gameren, J E Bugaj, J Erion, M Schmidt, A Srinivasan, E P Krenning
• Journal: International journal of cancer (Int J Cancer) Vol. 92 Issue 5 Pg. 628-33 (Jun 01 2001) ISSN: 0020-7136 [Print] United States
• PMID: 11340564 (Publication Type: Journal Article)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• Chelating Agents
• Radioisotopes
• Receptors, Somatostatin
• 3-Tyr-octreotide
• Lutetium
• Octreotide

Topics

• Animals
• Autoradiography
• Chelating Agents (therapeutic use)
• Kidney (metabolism)
• Lutetium (therapeutic use)
• Male
• Octreotide (analogs & derivatives, therapeutic use)
• Pancreatic Neoplasms (metabolism, mortality, radiotherapy)
• Radioisotopes (therapeutic use)
• Radiotherapy Dosage
• Rats
• Rats, Inbred Lew
• Receptors, Somatostatin (analysis)
• Survival Rate
• Tissue Distribution