Sci-Fri AM General-07: Dual Isotope SPECT to Track Transplanted Cells in Canine Myocardium Using Molecular Imaging

Introduction: Non‐invasive cell tracking techniques that provide repetitive and functional assessments of transplanted cells will be an asset in cell‐based therapies. Specifically, reporter gene (RG) expression may be used to signal certain molecular events as they occur in vivo. Objective: To compare the in vivo kinetics of a radiolabeled reporter probe (RP) specifically targeted by RG expression to a non‐specific radiolabel (NSL) in canine bone marrow cells (BMC). Cells were co‐labeled in vitro, transplanted into normal canine myocardium, and tracked using dual‐isotope SPECT. Methods: Following canine bone marrow harvest (n=1), BMCs were isolated, transfected with RG, and grown in culture for 4 weeks. Transfected cells (5.4×106) were then incubated with RP and NSL followed by direct injection into the left canine ventricle. The recipient of transplanted cells was also the donor. Forty 1‐hr SPECTimages were acquired to obtain washout kinetics of RP and NSL. Time activity curves (TAC) were generated from SPECT region of interest analysis. After sacrifice, ex vivo measurements of RP and NSL activity remaining in the myocardium were made with a high purity germanium gamma‐ray well counter. Results: Decay‐corrected TACs demonstrated faster washout kinetics for RP compared to NSL with biological half‐lives of 19 and 39 hours, respectively. This suggests that RP loss is greater than that attributed to cell death alone and demonstrates differences in label stability. Ex vivotissue analysis confirmed these results. Conclusion: Multispectral SPECT shows potential for monitoring RG stability and expression to follow cell viability and function non‐invasively in large animals.