Prolonged Cardiac Allograft Survival Using Iodine 131 After Human Sodium Iodide Symporter Gene Transfer in A Rat Model

D. Ricci, A. A. Mennander, N. Miyagi, V. P. Rao, H. D. Tazelaar, K. Classic, G. W. Byrne, Stephen J Russell, C. G A McGregor

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Abstract

Background: Radioiodine is efficiently concentrated by tissues expressing the human sodium iodide symporter (hNIS). Objective: To analyze the effects of iodine 131 on acute cardiac allograft rejection after ex vivo hNIS gene transfer in a rat model of cardiac allotransplantation. Materials and Methods: Hearts from Brown Norway rats were perfused ex vivo either with UW (University of Wisconsin) solution (n = 9) or UW solution containing 1 × 109 pfu/mL of adenovirus 5 plus NIS (Ad-NIS) (n = 18). Donor hearts were transplanted heterotopically into the abdomen of Lewis rats, and recipients were treated on postoperative day 3 with either 15,000 μCi of 131I or saline solution. The hearts were explanted when no longer beating, and were evaluated histologically for evidence of rejection and other changes. Results: Grafts perfused with the Ad-NIS vector survived significantly longer in recipients injected with 131I (mean [SD], 11.3 [1.9] days) compared with control animals not treated with 131I (5.7 [0.65] days) (P < .001). Treatment with 131I did not prolong graft survival in recipients of hearts that were not perfused with Ad-NIS (5.5 [1.0] vs 5.3 [0.8] days). In Ad-NIS 131I-treated transplants, the level of myocardial damage on day 6 after surgery, when control hearts were rejected, was significantly lower (60.8 [28.0] vs 99.7 [0.8]; P < .05). Conclusion: Our findings indicate that 131I, after NIS gene transfer, can effectively prolong cardiac allograft survival. To our knowledge, this is the first report of the use of NIS-targeted 131I therapy in cardiac transplantation. Further studies are required to determine the mechanism of this effect and its potential for clinical application.

Original languageEnglish (US)
Pages (from-to)1888-1894
Number of pages7
JournalTransplantation Proceedings
Volume42
Issue number5
DOIs
StatePublished - Jun 2010

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Iodine
Allografts
Adenoviridae
Genes
Transplants
Graft Survival
Heart Transplantation
Sodium Chloride
Abdomen
sodium-iodide symporter
Therapeutics

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Ricci, D., Mennander, A. A., Miyagi, N., Rao, V. P., Tazelaar, H. D., Classic, K., ... McGregor, C. G. A. (2010). Prolonged Cardiac Allograft Survival Using Iodine 131 After Human Sodium Iodide Symporter Gene Transfer in A Rat Model. Transplantation Proceedings, 42(5), 1888-1894. https://doi.org/10.1016/j.transproceed.2009.12.065

Prolonged Cardiac Allograft Survival Using Iodine 131 After Human Sodium Iodide Symporter Gene Transfer in A Rat Model. / Ricci, D.; Mennander, A. A.; Miyagi, N.; Rao, V. P.; Tazelaar, H. D.; Classic, K.; Byrne, G. W.; Russell, Stephen J; McGregor, C. G A.

In: Transplantation Proceedings, Vol. 42, No. 5, 06.2010, p. 1888-1894.

Research output: Contribution to journalArticle

Ricci, D, Mennander, AA, Miyagi, N, Rao, VP, Tazelaar, HD, Classic, K, Byrne, GW, Russell, SJ & McGregor, CGA 2010, 'Prolonged Cardiac Allograft Survival Using Iodine 131 After Human Sodium Iodide Symporter Gene Transfer in A Rat Model', Transplantation Proceedings, vol. 42, no. 5, pp. 1888-1894. https://doi.org/10.1016/j.transproceed.2009.12.065
Ricci, D. ; Mennander, A. A. ; Miyagi, N. ; Rao, V. P. ; Tazelaar, H. D. ; Classic, K. ; Byrne, G. W. ; Russell, Stephen J ; McGregor, C. G A. / Prolonged Cardiac Allograft Survival Using Iodine 131 After Human Sodium Iodide Symporter Gene Transfer in A Rat Model. In: Transplantation Proceedings. 2010 ; Vol. 42, No. 5. pp. 1888-1894.
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abstract = "Background: Radioiodine is efficiently concentrated by tissues expressing the human sodium iodide symporter (hNIS). Objective: To analyze the effects of iodine 131 on acute cardiac allograft rejection after ex vivo hNIS gene transfer in a rat model of cardiac allotransplantation. Materials and Methods: Hearts from Brown Norway rats were perfused ex vivo either with UW (University of Wisconsin) solution (n = 9) or UW solution containing 1 × 109 pfu/mL of adenovirus 5 plus NIS (Ad-NIS) (n = 18). Donor hearts were transplanted heterotopically into the abdomen of Lewis rats, and recipients were treated on postoperative day 3 with either 15,000 μCi of 131I or saline solution. The hearts were explanted when no longer beating, and were evaluated histologically for evidence of rejection and other changes. Results: Grafts perfused with the Ad-NIS vector survived significantly longer in recipients injected with 131I (mean [SD], 11.3 [1.9] days) compared with control animals not treated with 131I (5.7 [0.65] days) (P < .001). Treatment with 131I did not prolong graft survival in recipients of hearts that were not perfused with Ad-NIS (5.5 [1.0] vs 5.3 [0.8] days). In Ad-NIS 131I-treated transplants, the level of myocardial damage on day 6 after surgery, when control hearts were rejected, was significantly lower (60.8 [28.0] vs 99.7 [0.8]; P < .05). Conclusion: Our findings indicate that 131I, after NIS gene transfer, can effectively prolong cardiac allograft survival. To our knowledge, this is the first report of the use of NIS-targeted 131I therapy in cardiac transplantation. Further studies are required to determine the mechanism of this effect and its potential for clinical application.",
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