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.