Sodium iodide symporter (hNIS) permits molecular imaging of gene transduction in cardiac transplantation.
BACKGROUND
We evaluated the feasibility of noninvasive micro-single photon emission computed tomography (SPECT)/computed tomography (CT) imaging and quantification of cardiac gene expression after sodium iodide symporter (hNIS) gene transfer in cardiac transplantation.


METHODS
Donor rat hearts were perfused ex vivo with adenovirus expressing hNIS (Ad-hNIS), Ad-Null, or University of Wisconsin (UW) solution prior to heterotopic transplantation into syngeneic recipients. In the first group of recipients, imaging of the transplanted hearts with micro-SPECT/CT on day 5 was followed by immediate explant of the organs for ex vivo analyses. Radioactivity counts in the explanted hearts were obtained ex vivo and expressed as a percentage of the injected dose per gram of tissue (%ID/g). Intensities of the SPECT images of the transplanted hearts were quantified and converted to radioactive counts using a standard equation. The second group of recipients was imaged sequentially after injection of I on days 2 to 14 after transplantation.


RESULTS
Higher ex vivo radioiodine counts were noted in the hearts perfused with Ad-hNIS (1.04+/-0.2) compared to either the UW group (0.31+/-0.11, P<0.001) or the Ad-Null group (0.32+/-0.08, P<0.001). Image intensity in the Ad-NIS group (0.9+/-0.2) was also significantly higher than in the UW group (0.4+/-.03, P=0.003) or the Ad-Null group (0.5+/-0.1, P<0.05). Sequential imaging of Ad-NIS-perfused hearts between postoperative days 2 and 14 revealed peak image intensity at day 5. Overall, image intensities correlated with ex vivo counts of radioactivity (rho=0.74, P<0.05).


CONCLUSIONS
These data demonstrate that hNIS gene transfer permits sequential real-time detection and quantification of reporter gene expression in the transplanted heart with micro-SPECT/CT imaging.
Rao
Vinay P
VP
William J. von Liebig Transplant Center, Department of Surgery, Division of Cardiovascular Surgery, Mayo Clinic, Rochester, MN, USA.
Miyagi
Naoto
N
Ricci
Davide
D
Carlson
Stephanie K
SK
Morris
John C
JC
Federspiel
Mark J
MJ
Bailey
Kent R
KR
Russell
Stephen J
SJ
McGregor
Christopher G A
CG
D000818:Animals; D018014:Gene Transfer Techniques; D006321:Heart / Q000000981:diagnostic imaging*; D016027:Heart Transplantation / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D049268:Positron-Emission Tomography; D051381:Rats; D011917:Rats, Inbred Lew; D027981:Symporters / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D014161:Transduction, Genetic; D014185:Transplantation, Isogeneic; D000099209:Sodium-Iodide Symporters
D027981:Symporters; D000099209:Sodium-Iodide Symporters