The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1272-1281
Number of pages10
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume35
Issue number7
DOIs
StatePublished - Jul 2008

Fingerprint

Radioisotopes
Prostatic Neoplasms
Therapeutic Uses
Prostate-Specific Antigen
Iodides
Neoplasms
Therapeutics
Tumor Burden
Genes
Half-Life
Injections
Growth
In Vitro Techniques

Keywords

  • At therapy
  • Gene therapy
  • Prostate cancer
  • PSA promoter
  • Sodium iodide symporter

ASJC Scopus subject areas

  • Medicine(all)
  • Radiology Nuclear Medicine and imaging

Cite this

Willhauck, M. J., Samani, B. R. S., Wolf, I., Senekowitsch-Schmidtke, R., Stark, H. J., Meyer, G. J., ... Spitzweg, C. (2008). The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer. European Journal of Nuclear Medicine and Molecular Imaging, 35(7), 1272-1281. https://doi.org/10.1007/s00259-008-0775-4

The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer. / Willhauck, Michael J.; Samani, Bibi Rana Sharif; Wolf, Ingo; Senekowitsch-Schmidtke, Reingard; Stark, Hans Jürgen; Meyer, Geerd J.; Knapp, Wolfram H.; Göke, Burkhard; Morris, John C.; Spitzweg, Christine.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 35, No. 7, 07.2008, p. 1272-1281.

Research output: Contribution to journalArticle

Willhauck, MJ, Samani, BRS, Wolf, I, Senekowitsch-Schmidtke, R, Stark, HJ, Meyer, GJ, Knapp, WH, Göke, B, Morris, JC & Spitzweg, C 2008, 'The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer', European Journal of Nuclear Medicine and Molecular Imaging, vol. 35, no. 7, pp. 1272-1281. https://doi.org/10.1007/s00259-008-0775-4
Willhauck, Michael J. ; Samani, Bibi Rana Sharif ; Wolf, Ingo ; Senekowitsch-Schmidtke, Reingard ; Stark, Hans Jürgen ; Meyer, Geerd J. ; Knapp, Wolfram H. ; Göke, Burkhard ; Morris, John C. ; Spitzweg, Christine. / The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer. In: European Journal of Nuclear Medicine and Molecular Imaging. 2008 ; Vol. 35, No. 7. pp. 1272-1281.
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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.",
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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

PY - 2008/7

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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 - Prostate cancer

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