Effective cancer therapy with the alpha-particle emitter [211At]astatine in a mouse model of genetically modified sodium/iodide symporter-expressing tumors.
OBJECTIVE
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.


METHODS
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).


CONCLUSIONS
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.
Klinik für Nuklearmedizin, Medizinische Hochschule Hannover, Hanover, Germany.
Thorsten
T
Petrich
Leticia
L
Quintanilla-Martinez
Zekiye
Z
Korkmaz
Elenore
E
Samson
Hans Jürgen
HJ
Helmeke
Geerd Jürgen
GJ
Meyer
Wolfram H
WH
Knapp
Eyck
E
Pötter
D000818:Animals; D001246:Astatine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001284:Atrophy; D045744:Cell Line, Tumor; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D011877:Radionuclide Imaging; D016019:Survival Analysis; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000473:pathology / Q000528:radiation effects; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000099209:Sodium-Iodide Symporters
D001246:Astatine; D027981:Symporters; D000099209:Sodium-Iodide Symporters