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

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

Results: NIS-transfected LNCaP cells (NP-1) concentrated 8% of the total applied activity of ¹⁸⁸Re as compared to 16% of ¹²⁵I, 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% ID/g of ¹⁸⁸Re (t_1/2 biol. 12.9 h) which resulted in a 4.7-fold increased tumor absorbed dose (450 mGy/MBq) for ¹⁸⁸Re as compared to ¹³¹I. After application of 55.5 MBq of ¹³¹I or ¹⁸⁸Re, smaller tumors showed a similar average volume reduction of 86%, while in larger tumors volume reduction was significantly increased from 73% after ¹³¹I treatment to 85% after application of ¹⁸⁸Re.

Conclusion: While in smaller prostate cancer xenografts both radionuclides seemed to be equally effective after PSA-promoter-mediated NIS gene delivery, a superior therapeutic effect has been demonstrated for ¹⁸⁸Re in larger tumors.