Rhenium-188 as an alternative to Iodine-131 for treatment of prostate cancer following tissue-specific sodium iodide symporter gene transfer

We reported recently the induction of selective iodide uptake activity in prostate cancer cells (LNCaP) by prostate-specific antigen (PSA) promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of I-131. These data demonstrated the enormous potential of the NIS gene as novel therapeutic gene for treatment of non-thyroidal tumors, although in some non-thyroidal tumors therapeutic efficacy may be limited by rapid iodide efflux due to lack of iodide organification. In the current study, we therefore studied the potential of Re-188, as an alternative radionuclide, also transported by NIS, with a shorter half-life (17h) and higher energy beta particles with a longer path length (23–32mm) than I-131 (half-life 8d, path length 2.6–5mm). For this purpose xenografts from LNCaP cells stably expressing NIS under the control of the PSA-promoter (NP-1) in athymic nude mice were imaged using a gamma camera after i.p. injection of I-123 or Re-188. While 25–30% of the total I-123 dose was accumulated in NP-1 tumors with a biological half-life of 45h, 8–16% of Re-188 was accumulated with a biological half-life of 13h. Considering a tumor mass of 1g, the tumor absorbed dose was calculated to be approx. 448 mGy/MBq after Re-188 application, which was 4.7 times higher than for I-131 (94.5 mGy/MBq). After a single i.p. application of 55.5 MBq of I-131 or Re-188, smaller tumors (<0.2cm³, mean volume 0.138cm³ (I-131-group) and 0.121cm³ (Re-188-group)) showed a significant tumor volume reduction of up to 90% and 83%, respectively. In larger tumors (>0.2cm³, mean volume 0.472cm³ (I-131-group) and 0.466cm³ (Re-188-group)), tumor volume reduction, which was 72% in the I-131-treated group, was significantly increased to 85% after application of Re-188 (p<0.05).

In conclusion, while therapeutic efficacy of Re-188 and I-131 seems to be similar in smaller prostate cancer xenografts after PSA-promoter-mediated NIS gene delivery, a superior therapeutic effect was demonstrated for Re-188 in larger tumors.