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

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 (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.

• Authors: 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
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 35 Issue 7 Pg. 1272-81 (Jul 2008) ISSN: 1619-7070 [Print] Germany
• PMID: 18404268 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Symporters
• sodium-iodide symporter
• Prostate-Specific Antigen
• Astatine

Topics

• Animals
• Astatine (administration & dosage, pharmacokinetics, therapeutic use)
• Cell Line, Tumor
• Humans
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Promoter Regions, Genetic
• Prostate-Specific Antigen (genetics)
• Prostatic Neoplasms (genetics, metabolism, radiotherapy)
• Recombinant Proteins (genetics, metabolism)
• Symporters (genetics, metabolism)
• Transfection
• Transplantation, Heterologous
• Tumor Stem Cell Assay