Application of 188Rhenium 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 (131)iodine ( I-131). 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 ( Re-188), as an alternative radionuclide, also transported by NIS, with a shorter half- life and higher energy beta- particles than I-131. Results: NIS- transfected LNCaP cells ( NP- 1) concentrated 8% of the total applied activity of Re-188 as compared with 16% of I-125, 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 Re-188 ( biological half- life 12.9 h), which resulted in a 4.7- fold increased tumor absorbed dose ( 450 mGy/ MBq) for Re-188 as compared with I-131. After application of 55.5 MBq I-131 or Re-188, smaller tumors showed a similar average volume reduction of 86%, whereas in larger tumors volume reduction was significantly increased from 73% after I-131 treatment to 85% after application of Re-188. 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 Re-188 in larger tumors.