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

Research output: Contribution to journalArticle

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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

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Gene expression
Radioisotopes
Tumors
Prostatic Neoplasms
Iodides
Therapeutic Uses
Gene Expression
Prostate-Specific Antigen
Heterografts
Genes
Half-Life
Neoplasms
Tumor Burden
Nude Mice
Assays
Cameras
Cells
sodium-iodide symporter
Therapeutics
Imaging techniques

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Medicine(all)
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Application of 188rhenium as an alternative radionuclide for treatment of prostate cancer after tumor-specific sodium iodide symporter gene expression. / Willhauck, Michael J.; Samani, Bibi Rana Sharif; Gildehaus, Franz Josef; Wolf, Ingo; Senekowitsch-Schmidtke, Reingard; Stark, Hans Jürgen; Göke, Burkhard; Morris, John C.; Spitzweg, Christine.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 11, 11.2007, p. 4451-4458.

Research output: Contribution to journalArticle

Willhauck, MJ, Samani, BRS, Gildehaus, FJ, Wolf, I, Senekowitsch-Schmidtke, R, Stark, HJ, Göke, B, Morris, JC & 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, vol. 92, no. 11, pp. 4451-4458. https://doi.org/10.1210/jc.2007-0402
Willhauck, Michael J. ; Samani, Bibi Rana Sharif ; Gildehaus, Franz Josef ; Wolf, Ingo ; Senekowitsch-Schmidtke, Reingard ; Stark, Hans Jürgen ; Göke, Burkhard ; Morris, John C. ; Spitzweg, Christine. / Application of 188rhenium as an alternative radionuclide for treatment of prostate cancer after tumor-specific sodium iodide symporter gene expression. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 11. pp. 4451-4458.
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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.",
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AU - Willhauck, Michael J.

AU - Samani, Bibi Rana Sharif

AU - Gildehaus, Franz Josef

AU - Wolf, Ingo

AU - Senekowitsch-Schmidtke, Reingard

AU - Stark, Hans Jürgen

AU - Göke, Burkhard

AU - Morris, John C.

AU - Spitzweg, Christine

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N2 - 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.

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