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(Circulation. 2003;108:1302.)
© 2003 American Heart Association, Inc.

Brief Rapid Communications

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

Joseph C. Wu, MD; Ian Y. Chen, MSE; Gobalakrishnan Sundaresan, PhD; Jung-Joon Min, MD; Abhijit De, PhD; Jian-Hua Qiao, MD; Michael C. Fishbein, MD; Sanjiv S. Gambhir, MD, PhD

From the Department of Molecular and Medical Pharmacology and Crump Institute for Molecular Imaging (J.C.W., I.Y.C., J.J.M., G.S., A.D., S.S.G.), the Department of Pathology (J.H.Q., M.C.F.), and the Department of Medicine, Division of Cardiology (J.C.W.), UCLA School of Medicine, Los Angeles, Calif; and the Department of Radiology and Bio-X Program (S.S.G.), Stanford University, Stanford, Calif.

Correspondence to Sanjiv Gambhir, The James H. Clark Center, 318 Campus Dr, East Wing, First Floor, Stanford, CA 94305-5427. E-mail sgambhir{at}stanford.edu

Received April 23, 2003; de novo received June 24, 2003; revision received July 24, 2003; accepted July 26, 2003.

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 (3x10⁶ to 5x10⁵) expressing firefly luciferase (Fluc) reporter gene. Cardiac bioluminescence signals were present for more than 2 weeks with 3x10⁶ 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 (3x10⁶) expressing mutant herpes simplex type 1 thymidine kinase (HSV1-sr39tk) reporter gene. Detailed tomography of transplanted cells is shown by 9-(4-[¹⁸F]-fluoro-3hydroxymethylbutyl)guanine ([¹⁸F]-FHBG) reporter probe and nitrogen-13 ammonia ([¹³N]-NH₃) perfusion images. Within the transplanted region, there was a 4.48±0.71-fold increase of in vivo [¹⁸F]-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.

Key Words: transplantation • heart failure • genes • imaging • nuclear medicine

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