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

J Clin Endocrinol Metab. 2007 Nov;92(11):4451-8. doi: 10.1210/jc.2007-0402. Epub 2007 Aug 14.


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 (131)iodine ((131)I). 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 (188)rhenium ((188)Re), as an alternative radionuclide, also transported by NIS, with a shorter half-life and higher energy beta-particles than (131)I.

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

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 (188)Re in larger tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Line, Tumor
  • Cell Survival / genetics
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation, Neoplastic / genetics*
  • Half-Life
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Prostate-Specific Antigen / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / radiotherapy*
  • Radioisotopes / pharmacokinetics
  • Radioisotopes / therapeutic use
  • Rhenium / pharmacokinetics
  • Rhenium / therapeutic use*
  • Symporters / genetics*
  • Tumor Stem Cell Assay
  • Xenograft Model Antitumor Assays


  • Iodine Radioisotopes
  • Radioisotopes
  • Symporters
  • sodium-iodide symporter
  • Rhenium
  • Prostate-Specific Antigen