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