Intravenous administration of 90Y-labeled polyoxazoline combined with tumor heating potently inhibits tumor growth in mice

Abstract

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 (¹¹¹In)-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 ¹¹¹In-labeled POZ and the antitumor effects of radionuclide therapy using yttrium-90 (⁹⁰Y)-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 ⁹⁰Y-labeled POZ, a marked dose-dependent therapeutic effect of radioactivity was observed in the groups treated with ⁹⁰Y-POZ combined with tumor heating with no obvious systemic side effects. These results demonstrated that thermoresponsive ⁹⁰Y-labeled POZ showed a potent therapeutic effect in combination with tumor heating, suggesting the usefulness for radionuclide therapy of tumors.

Keywords: Drug delivery system; Hyperthermia; Polyoxazoline; Radionuclide therapy; Thermoresponsive polymer.