[177Lu-DOTA(0),Tyr3] octreotate for somatostatin receptor-targeted radionuclide therapy

Int J Cancer. 2001 Jun 1;92(5):628-33. doi: 10.1002/1097-0215(20010601)92:5<628::aid-ijc1244>3.0.co;2-l.


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.

MeSH terms

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


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