The basic requirements for the development of radiopharmaceuticals for radionuclide therapy of tumors include marked tumor-specific accumulation and long-term intratumoral retention. We have previously reported an indium-111 (In)-labeled thermoresponsive polymer (polyoxazoline (POZ)) that is soluble at body temperature with rapid clearance from normal tissues but self-aggregates in the tumor upon tumor heating treatment. POZ accumulated in the tumor via self-aggregation under hyperthermic conditions and was retained after stopping heat exposure. In this study, we investigated the cellular uptake of In-labeled POZ and the antitumor effects of radionuclide therapy using yttrium-90 (Y)-labeled POZ in combination with tumor heating. A POZ derivative with a lower critical solution temperature (LCST) of 38 °C was efficiently taken up by Colon-26 tumor cells at temperatures above the LCST via phagocytosis. In the therapeutic study using Y-labeled POZ, a marked dose-dependent therapeutic effect of radioactivity was observed in the groups treated with Y-POZ combined with tumor heating with no obvious systemic side effects. These results demonstrated that thermoresponsive Y-labeled POZ showed a potent therapeutic effect in combination with tumor heating, suggesting the usefulness for radionuclide therapy of tumors.

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http://dx.doi.org/10.1016/j.ijpharm.2024.125103DOI Listing

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