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Tumor response after [(90)Y-DOTA(0),Tyr(3)]octreotide radionuclide therapy in a transplantable rat tumor model is dependent on tumor size.

AbstractUNLABELLED:
A promising application of radiolabeled somatostatin analogs is peptide receptor-targeted radionuclide therapy of somatostatin receptor-expressing tumors. A suitable radionuclide is (90)Y, which emits high-energy beta-particles with a pathlength of several millimeters in tissue, making it especially promising for treatment of large tumors.
METHODS:
We investigated the radiotherapeutic effect of different activities (111 and 370 MBq) of [(90)Y-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)(0),Tyr(3)]octreotide in Lewis rats bearing somatostatin receptor-positive rat pancreatic CA20948 tumors of different size (0.08-15 cm(2)) in their flank.
RESULTS:
Dose-dependent radiotherapeutic effects of (90)Y-labeled octreotide in this rat tumor model were found. Tumor control (100% complete response) was found in animals bearing tumors of 3-9 cm(2) (mean, 7.8 cm(2)) after intravenous injection of the highest activity (370 MBq [(90)Y-DOTA(0),Tyr(3)]octreotide). In rats bearing tumors of < or =1 cm(2) or > or =14 cm(2), the effects were less pronounced (50% and 0% complete response, respectively). In tumors of < or =1 cm(2) the (90)Y radiation energy will not be absorbed completely in the tumor, whereas in tumors of > or =14 cm(2) the increased number of clonogenic and probably hypoxic tumor cells may explain the failure to reach a cure.
CONCLUSION:
This study shows the ability of [(90)Y-DOTA(0),Tyr(3)]octreotide to control tumor growth, especially in medium-sized tumors. The effect of radionuclide therapy appeared to be dependent on tumor size at the onset of therapy.
AuthorsM de Jong, W A Breeman, B F Bernard, W H Bakker, T J Visser, P P Kooij, A van Gameren, E P Krenning
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 42 Issue 12 Pg. 1841-6 (Dec 2001) ISSN: 0161-5505 [Print] United States
PMID11752083 (Publication Type: Journal Article)
Chemical References
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • Yttrium Radioisotopes
  • octreotide, DOTA-Tyr(3)-
  • Octreotide
Topics
  • Animals
  • Dose-Response Relationship, Radiation
  • Male
  • Neoplasm Transplantation
  • Octreotide (analogs & derivatives, therapeutic use)
  • Pancreatic Neoplasms (mortality, radiotherapy)
  • Radiopharmaceuticals (therapeutic use)
  • Rats
  • Rats, Inbred Lew
  • Receptors, Somatostatin (radiation effects)
  • Yttrium Radioisotopes (therapeutic use)

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