부산대학교 도서관

Purpose We reported recently the induction of selective iodide uptake in prostate cancer cells (LNCaP) by prostate-specific antigen (PSA) promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of 131.sup.I. In the current study, we studied the potential of the high-energy alpha-emitter 211.sup.At, also transported by NIS, as an alternative radionuclide after NIS gene transfer in tumors with limited therapeutic efficacy of 131.sup.I due to rapid iodide efflux. Methods We investigated uptake and therapeutic efficacy of 211.sup.At in LNCaP cells stably expressing NIS under the control of the PSA promoter (NP-1) in vitro and in vivo. Results NP-1 cells concentrated 211.sup.At in a perchlorate-sensitive manner, which allowed a dramatic therapeutic effect in vitro. After intrapertoneal injection of 211.sup.At (1 MBq), NP-1 tumors accumulated approximately 16% ID/g 211.sup.At (effective half-life 4.6 h), which resulted in a tumor-absorbed dose of 1,580+-345 mGy/MBq and a significant tumor volume reduction of up to 82+-19%, while control tumors continued their growth exponentially. Conclusions A significant therapeutic effect of 211.sup.At has been demonstrated in prostate cancer after PSA promoter-directed NIS gene transfer in vitro and in vivo suggesting a potential role for 211.sup.At as an attractive alternative radioisotope for NIS-targeted radionuclide therapy, in particular in smaller tumors with limited radionuclide retention time.