Molecular Imaging of Cardiac Cell Transplantation in Living Animals Using Optical Bioluminescence and Positron Emission Tomography

Abstract

Background— The current method of analyzing myocardial cell transplantation relies on postmortem histology. We sought to demonstrate the feasibility of monitoring transplanted cell survival in living animals using molecular imaging techniques. Methods and Results— For optical bioluminescence charged-coupled device imaging, rats (n=20) underwent intramyocardial injection of embryonic rat H9c2 cardiomyoblasts (3×10 6 to 5×10 5 ) expressing firefly luciferase (Fluc) reporter gene. Cardiac bioluminescence signals were present for more than 2 weeks with 3×10 6 cells: day 1 (627 000±15%), day 2 (346 100±21%), day 4 (112 800±20%), day 8 (78 860±24%), day 12 (67 780±12%), and day 16 (62 200±5% p · s −1 · cm 2 −1 · sr −1 ). For micro–positron emission tomography imaging, rats (n=20) received cardiomyoblasts (3×10 6 ) expressing mutant herpes simplex type 1 thymidine kinase (HSV1-sr39tk) reporter gene. Detailed tomography of transplanted cells is shown by 9-(4-[ 18 F]-fluoro-3hydroxymethylbutyl)guanine ([ 18 F]-FHBG) reporter probe and nitrogen-13 ammonia ([ 13 N]-NH 3 ) perfusion images. Within the transplanted region, there was a 4.48±0.71-fold increase of in vivo [ 18 F]-FHBG activity and a 4.01±0.51-fold increase of ex vivo gamma counting compared with control animals. Finally, the in vivo images of cell survival were confirmed by ex vivo autoradiography, histology, immunohistochemistry, and reporter protein assays. Conclusions— The location(s), magnitude, and survival duration of embryonic cardiomyoblasts were monitored noninvasively. With further development, molecular imaging studies should add critical insights into cardiac cell transplantation biology.