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Effective Cancer Therapy with the -Particle Emitter [²¹¹At]Astatine in a Mouse Model of Genetically Modified Sodium/Iodide Symporter–Expressing Tumors

Authors' Affiliations: ¹ Klinik für Nuklearmedizin, Medizinische Hochschule Hannover, Hanover, Germany; ² Institut für Pathologie, GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany

Requests for reprints: Eyck Pötter, Department of Nuclear Medicine, Medizinische Hochschule Hanover, Carl-Neuberg-Str.1, 30625 Hannover, Germany. E-mail: eyck.potter{at}web.de.

Purpose: The sodium/iodide symporter (NIS) gene is currently explored in several trials to eradicate experimental cancer with radiodine (¹³¹I) by its ß-emission. We recently characterized NIS-specific cellular uptake of an alternative halide, radioastatine (²¹¹At), which emits high-energy -particles. The aim of this study was to investigate in vivo effects of the high linear energy transfer (LET) emitter ²¹¹At on tumor growth and outcome in nude mice.

Experimental Design: We administered radioastatide in a fractionated therapy scheme to NMRI nude mice harboring rapidly growing solid tumors established from a papillary thyroid carcinoma cell line genetically modified to express NIS (K1-NIS). Animals were observed over 1 year. Tumor growth, body weight, blood counts, survival, and side effects were measured compared with control groups without therapy and/or lack of NIS expression.

Results: Within 3 months, radioastatide caused complete primary tumor eradication in all cases of K1-NIS tumor-bearing nude mice (n = 25) with no tumor recurrence during 1 year follow-up. Survival rates of the K1-NIS/²¹¹At group were 96% after 6 months and 60% after 1 year, in contrast to those of control groups (maximum survival 40 days).

Conclusion: Our study indicates that ²¹¹At represents a promising substrate for NIS-mediated therapy of various cancers either with endogenous or gene transfer-mediated NIS expression.