The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer.
OBJECTIVE
We reported recently the induction of selective iodide uptake in prostate cancer cells (LNCaP) by prostate-specific antigen (PSA) promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of (131)I. In the current study, we studied the potential of the high-energy alpha-emitter (211)At, also transported by NIS, as an alternative radionuclide after NIS gene transfer in tumors with limited therapeutic efficacy of (131)I due to rapid iodide efflux.


METHODS
We investigated uptake and therapeutic efficacy of (211)At in LNCaP cells stably expressing NIS under the control of the PSA promoter (NP-1) in vitro and in vivo.


RESULTS
NP-1 cells concentrated (211)At in a perchlorate-sensitive manner, which allowed a dramatic therapeutic effect in vitro. After intraperitoneal injection of (211)At (1 MBq), NP-1 tumors accumulated approximately 16% ID/g (211)At (effective half-life 4.6 h), which resulted in a tumor-absorbed dose of 1,580+/-345 mGy/MBq and a significant tumor volume reduction of up to 82+/-19%, while control tumors continued their growth exponentially.


CONCLUSIONS
A significant therapeutic effect of (211)At has been demonstrated in prostate cancer after PSA promoter-directed NIS gene transfer in vitro and in vivo suggesting a potential role for (211)At as an attractive alternative radioisotope for NIS-targeted radionuclide therapy, in particular in smaller tumors with limited radionuclide retention time.
Willhauck
Michael J
MJ
Department of Internal Medicine II, Ludwig-Maximilians-University, Munich, Germany.
Samani
Bibi-Rana Sharif
BR
Wolf
Ingo
I
Senekowitsch-Schmidtke
Reingard
R
Stark
Hans-Jürgen
HJ
Meyer
Geerd J
GJ
Knapp
Wolfram H
WH
Göke
Burkhard
B
Morris
John C
JC
Spitzweg
Christine
C
D000818:Animals; D001246:Astatine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous; D014410:Tumor Stem Cell Assay; D000099209:Sodium-Iodide Symporters
D001246:Astatine; D017430:Prostate-Specific Antigen; D011994:Recombinant Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters