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.
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.
Authors: Mohan Hingorani; Christine Spitzweg; Georges Vassaux; Kate Newbold; Alan Melcher; Hardev Pandha; Richard Vile; Kevin Harrington Journal: Curr Cancer Drug Targets Date: 2010-03 Impact factor: 3.428
Authors: Mohan Hingorani; Christine L White; Shane Zaidi; Hardev S Pandha; Alan A Melcher; Shreerang A Bhide; Christopher M Nutting; Konstantinos N Syrigos; Richard G Vile; Georges Vassaux; Kevin J Harrington Journal: Mol Ther Date: 2010-06-29 Impact factor: 11.454
Authors: Amanda J Weeks; Maite Jauregui-Osoro; Marcel Cleij; Julia E Blower; James R Ballinger; Philip J Blower Journal: Nucl Med Commun Date: 2011-02 Impact factor: 1.690
Authors: Maite Jauregui-Osoro; Kavitha Sunassee; Amanda J Weeks; David J Berry; Rowena L Paul; Marcel Cleij; Jasvinder Paul Banga; Michael J O'Doherty; Paul K Marsden; Susan E M Clarke; James R Ballinger; Istvan Szanda; Sheue-Yann Cheng; Philip J Blower Journal: Eur J Nucl Med Mol Imaging Date: 2010-06-25 Impact factor: 9.236