Application of 188rhenium as an alternative radionuclide for treatment of prostate cancer after tumor-specific sodium iodide symporter gene expression

Michael J. Willhauck, Bibi Rana Sharif Samani, Franz Josef Gildehaus, Ingo Wolf, Reingard Senekowitsch-Schmidtke, Hans Jürgen Stark, Burkhard Göke, John C. Morris, Christine Spitzweg

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42 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4451-4458
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number11
DOIs
StatePublished - Nov 2007

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Willhauck, M. J., Samani, B. R. S., Gildehaus, F. J., Wolf, I., Senekowitsch-Schmidtke, R., Stark, H. J., Göke, B., Morris, J. C., & Spitzweg, C. (2007). Application of 188rhenium as an alternative radionuclide for treatment of prostate cancer after tumor-specific sodium iodide symporter gene expression. Journal of Clinical Endocrinology and Metabolism, 92(11), 4451-4458. https://doi.org/10.1210/jc.2007-0402