Application of super(188)Rhenium as an Alternative Radionuclide for Treatment of Prostate Cancer after Tumor-Specific Sodium Iodide Symporter Gene Expression

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 super(131)iodine ( super(131)I). These data demonstrated the po...

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Published in:The journal of clinical endocrinology and metabolism 2007-11, Vol.92 (11), p.4451-4458
Main Authors: Willhauck, Michael J, Sharif Samani, Bibi-Rana, Gildehaus, Franz-Josef, Wolf, Ingo, Senekowitsch-Schmidtke, Reingard, Stark, Hans-Juergen, Goeke, Burkhard, Morris, John C, Spitzweg, Christine
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Language:English
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Summary: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 super(131)iodine ( super(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 super(188)rhenium ( super(188)Re), as an alternative radionuclide, also transported by NIS, with a shorter half-life and higher energy {szligbeta}-particles than super(131)I. RESULTS: NIS-transfected LNCaP cells (NP-1) concentrated 8% of the total applied activity of super(188)Re as compared with 16% of super(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 super(188)Re (biological half-life 12.9 h), which resulted in a 4.7-fold increased tumor absorbed dose (450 mGy/MBq) for super(188)Re as compared with super(131)I. After application of 55.5 MBq super(131)I or super(188)Re, smaller tumors showed a similar average volume reduction of 86%, whereas in larger tumors volume reduction was significantly increased from 73% after super(131)I treatment to 85% after application of super(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 super(188)Re in larger tumors.
ISSN:0021-972X