Effective cancer therapy with the alpha-particle emitter [211At]astatine in a mouse model of genetically modified sodium/iodide symporter-expressing tumors.
2006; American Association for Cancer Research; Volume: 12; Issue: 4 Linguagem: Inglês
10.1158/1078-0432.ccr-05-1576
ISSN1557-3265
AutoresT. Petrich, Leticia Quintanilla‐Martínez, Zekiye Korkmaz, Elenore Samson, Hans J√orgen Helmeke, G.-J. Meyer, Wolfram H. Knapp, Eyck P√∂tter,
Tópico(s)Radiation Therapy and Dosimetry
ResumoAbstract PURPOSE: The sodium/iodide symporter (NIS) gene is currently explored in several trials to eradicate experimental cancer with radiodine ((131)I) by its beta-emission. We recently characterized NIS-specific cellular uptake of an alternative halide, radioastatine ((211)At), which emits high-energy alpha-particles. The aim of this study was to investigate in vivo effects of the high linear energy transfer (LET) emitter (211)At 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/(211)At 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 (211)At represents a promising substrate for NIS-mediated therapy of various cancers either with endogenous or gene transfer-mediated NIS expression.
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