TY - JOUR
T1 - The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer
AU - Willhauck, Michael J.
AU - Samani, Bibi Rana Sharif
AU - Wolf, Ingo
AU - Senekowitsch-Schmidtke, Reingard
AU - Stark, Hans Jürgen
AU - Meyer, Geerd J.
AU - Knapp, Wolfram H.
AU - Göke, Burkhard
AU - Morris, John C.
AU - Spitzweg, Christine
N1 - Funding Information:
Acknowledgments The authors are grateful to S. M. Jhiang, Ph.D., Ohio State University, Columbus, OH, USA, for supplying the full-length human NIS cDNA. Further, the authors thank D.J. Tindall, Ph.D. and C.Y.F. Young, Ph.D., Department of Urology, Mayo Clinic, Rochester, MN, for providing the PSA promoter and the LNCaP prostate cancer cell line. This study was supported by grants to C. Spitzweg (Sp 581/3-2, Sp 581/4-1, Sp 581/4-2 [Forschergruppe FOR-411 ‘Radionuklidtherapie’]) from the Deutsche Forschungsgemeinschaft, Bonn, Germany, by the FöFoLe-Program of the Ludwig-Maximilians-University Munich to M.J. Willhauck (FöFoLe Reg. Nr. 442), and by the Mayo Foundation Prostate Cancer SPORE grant (CA91956) to J. C. Morris. The authors declare that the experiments comply with the current law of Germany. Animal experiments were approved by the regional governmental commission for animal protection.
PY - 2008/7
Y1 - 2008/7
N2 - 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.
AB - 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.
KW - At therapy
KW - Gene therapy
KW - PSA promoter
KW - Prostate cancer
KW - Sodium iodide symporter
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U2 - 10.1007/s00259-008-0775-4
DO - 10.1007/s00259-008-0775-4
M3 - Article
C2 - 18404268
AN - SCOPUS:45049086826
SN - 1619-7070
VL - 35
SP - 1272
EP - 1281
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 7
ER -