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Application of ¹⁸⁸Rhenium as an Alternative Radionuclide for Treatment of Prostate Cancer after Tumor-Specific Sodium Iodide Symporter Gene Expression

Departments of Internal Medicine II (M.J.W., B.-R.S.S., B.G., C.S.) and Nuclear Medicine (F.-J.G.), Ludwig-Maximilians-University, 81377 Munich, Germany; Department of Nuclear Medicine (I.W., R.S.-S.), Technical University Munich, 80333 Munich, Germany; Department of Carcinogenesis of the Skin (H.-J.S.), German Cancer Research Center, 69120 Heidelberg, Germany; and Division of Endocrinology (J.C.M.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Christine Spitzweg, M.D., Klinikum Grosshadern, Medizinische Klinik II, Marchioninistrasse 15, 81377 Muenchen, Germany. E-mail: Christine.Spitzweg{at}med.uni-muenchen.de.

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 ß-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. -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.