Erschienen in:
01.07.2008 | Original Article
The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer
verfasst von:
Michael J. Willhauck, Bibi-Rana Sharif Samani, Ingo Wolf, Reingard Senekowitsch-Schmidtke, Hans-Jürgen Stark, Geerd J. Meyer, Wolfram H. Knapp, Burkhard Göke, John C. Morris, Christine Spitzweg
Erschienen in:
European Journal of Nuclear Medicine and Molecular Imaging
|
Ausgabe 7/2008
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Abstract
Purpose
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 131I. In the current study, we studied the potential of the high-energy alpha-emitter 211At, also transported by NIS, as an alternative radionuclide after NIS gene transfer in tumors with limited therapeutic efficacy of 131I due to rapid iodide efflux.
Methods
We investigated uptake and therapeutic efficacy of 211At 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 211At in a perchlorate-sensitive manner, which allowed a dramatic therapeutic effect in vitro. After intrapertoneal injection of 211At (1 MBq), NP-1 tumors accumulated approximately 16% ID/g 211At (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 211At has been demonstrated in prostate cancer after PSA promoter-directed NIS gene transfer in vitro and in vivo suggesting a potential role for 211At as an attractive alternative radioisotope for NIS-targeted radionuclide therapy, in particular in smaller tumors with limited radionuclide retention time.