Prolonged cardiac allograft survival using iodine 131 after human sodium iodide symporter gene transfer in a rat model.
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.


METHODS
Hearts from Brown Norway rats were perfused ex vivo either with UW (University of Wisconsin) solution (n = 9) or UW solution containing 1 x 10(9) 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 microCi of (131)I 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 (131)I (mean [SD], 11.3 [1.9] days) compared with control animals not treated with (131)I (5.7 [0.65] days) (P < .001). Treatment with (131)I 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 (131)I-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).


CONCLUSIONS
Our findings indicate that (131)I, after NIS gene transfer, can effectively prolong cardiac allograft survival. To our knowledge, this is the first report of the use of NIS-targeted (131)I therapy in cardiac transplantation. Further studies are required to determine the mechanism of this effect and its potential for clinical application.
Ricci
D
D
Mayo Clinic William J. von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. dricci@molinette.piemonte.it
Mennander
A A
AA
Miyagi
N
N
Rao
V P
VP
Tazelaar
H D
HD
Classic
K
K
Byrne
G W
GW
Russell
S J
SJ
McGregor
C G A
CG
D000005:Abdomen / Q000000981:diagnostic imaging; D000818:Animals; D018014:Gene Transfer Techniques; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D007457:Iodine Radioisotopes; D023421:Models, Animal; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D027981:Symporters / Q000235:genetics* / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon; D016042:Transplantation, Heterotopic / Q000379:methods; D014184:Transplantation, Homologous / Q000502:physiology*; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters