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


CONCLUSIONS
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.
Willhauck
Michael J
MJ
Department of Internal Medicine II, Ludwig-Maximilians-University, 81377 Munich, Germany. .
Sharif Samani
Bibi-Rana
BR
Gildehaus
Franz-Josef
FJ
Wolf
Ingo
I
Senekowitsch-Schmidtke
Reingard
R
Stark
Hans-Jürgen
HJ
Göke
Burkhard
B
Morris
John C
JC
Spitzweg
Christine
C
D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006207:Half-Life; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use*; D027981:Symporters / Q000235:genetics*; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D017430:Prostate-Specific Antigen; D011868:Radioisotopes; D012211:Rhenium; D027981:Symporters; D000099209:Sodium-Iodide Symporters