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Tumor Response After [⁹⁰Y-DOTA⁰,Tyr³]Octreotide Radionuclide Therapy in a Transplantable Rat Tumor Model Is Dependent on Tumor Size

Departments of Nuclear Medicine and Internal Medicine III, University Hospital and Erasmus University Rotterdam, Rotterdam, The Netherlands

A promising application of radiolabeled somatostatin analogs is peptide receptor–targeted radionuclide therapy of somatostatin receptor–expressing tumors. A suitable radionuclide is ⁹⁰Y, which emits high-energy ß-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 [⁹⁰Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)⁰,Tyr³]octreotide in Lewis rats bearing somatostatin receptor–positive rat pancreatic CA20948 tumors of different size (0.08–15 cm²) in their flank. Results: Dose-dependent radiotherapeutic effects of ⁹⁰Y-labeled octreotide in this rat tumor model were found. Tumor control (100% complete response) was found in animals bearing tumors of 3–9 cm² (mean, 7.8 cm²) after intravenous injection of the highest activity (370 MBq [⁹⁰Y-DOTA⁰,Tyr³]octreotide). In rats bearing tumors of 1 cm² or 14 cm², the effects were less pronounced (50% and 0% complete response, respectively). In tumors of 1 cm² the ⁹⁰Y radiation energy will not be absorbed completely in the tumor, whereas in tumors of 14 cm² 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 [⁹⁰Y-DOTA⁰,Tyr³]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.

Key Words: [⁹⁰Y-DOTA⁰,Tyr³]octreotide • peptide receptor radionuclide therapy • rat • tumor size • curability

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