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.
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.
Authors: Mohan Hingorani; Christine Spitzweg; Georges Vassaux; Kate Newbold; Alan Melcher; Hardev Pandha; Richard Vile; Kevin Harrington Journal: Curr Cancer Drug Targets Date: 2010-03 Impact factor: 3.428
Authors: Mohan Hingorani; Christine L White; Shane Zaidi; Hardev S Pandha; Alan A Melcher; Shreerang A Bhide; Christopher M Nutting; Konstantinos N Syrigos; Richard G Vile; Georges Vassaux; Kevin J Harrington Journal: Mol Ther Date: 2010-06-29 Impact factor: 11.454
Authors: Kerstin Knoop; Nathalie Schwenk; Patrick Dolp; Michael J Willhauck; Christoph Zischek; Christian Zach; Markus Hacker; Burkhard Göke; Ernst Wagner; Peter J Nelson; Christine Spitzweg Journal: Hum Gene Ther Date: 2013-03 Impact factor: 5.695