Application of 188rhenium as an alternative radionuclide for treatment of prostate cancer after tumor-specific sodium iodide symporter gene expression.

Abstract

CONTEXT:

We reported recently the induction of iodide accumulation in prostate cancer cells (LNCaP) by prostate-specific antigen promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of (131)iodine ((131)I). These data demonstrated the potential of the NIS gene as a novel therapeutic gene, although in some extrathyroidal tumors, therapeutic efficacy may be limited by rapid iodide efflux due to a lack of iodide organification.

OBJECTIVE:

In the current study, we therefore studied the potential of (188)rhenium ((188)Re), as an alternative radionuclide, also transported by NIS, with a shorter half-life and higher energy beta-particles than (131)I.

RESULTS:

NIS-transfected LNCaP cells (NP-1) concentrated 8% of the total applied activity of (188)Re as compared with 16% of (125)I, which was sufficient for a therapeutic effect in an in vitro clonogenic assay. gamma-Camera imaging of NP-1 cell xenografts in nude mice revealed accumulation of 8-16% injected dose (ID)/g (188)Re (biological half-life 12.9 h), which resulted in a 4.7-fold increased tumor absorbed dose (450 mGy/MBq) for (188)Re as compared with (131)I. After application of 55.5 MBq (131)I or (188)Re, smaller tumors showed a similar average volume reduction of 86%, whereas in larger tumors volume reduction was significantly increased from 73% after (131)I treatment to 85% after application of (188)Re.

CONCLUSION:

Although in smaller prostate cancer xenografts both radionuclides seemed to be equally effective after prostate-specific antigen promoter-mediated NIS gene delivery, a superior therapeutic effect has been demonstrated for (188)Re in larger tumors.

• Authors: Michael J Willhauck, Bibi-Rana Sharif Samani, Franz-Josef Gildehaus, Ingo Wolf, Reingard Senekowitsch-Schmidtke, Hans-Jürgen Stark, Burkhard Göke, John C Morris, Christine Spitzweg
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 92 Issue 11 Pg. 4451-8 (Nov 2007) ISSN: 0021-972X [Print] United States
• PMID: 17698909 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Iodine Radioisotopes
• Radioisotopes
• Symporters
• sodium-iodide symporter
• Rhenium
• Prostate-Specific Antigen

Topics

• Adult
• Animals
• Cell Line, Tumor
• Cell Survival (genetics)
• Fluorescent Antibody Technique, Indirect
• Gene Expression Regulation, Neoplastic (genetics)
• Half-Life
• Humans
• Iodine Radioisotopes (therapeutic use)
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Prostate-Specific Antigen (metabolism)
• Prostatic Neoplasms (genetics, metabolism, radiotherapy)
• Radioisotopes (pharmacokinetics, therapeutic use)
• Rhenium (pharmacokinetics, therapeutic use)
• Symporters (genetics)
• Tumor Stem Cell Assay
• Xenograft Model Antitumor Assays