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Cell Therapy in Murine Atherosclerosis: In Vivo Imaging with High-Resolution Helical SPECT¹

¹ From the Department of Medicine, Division of Cardiology (S.V., X.L., C.D., P.J.G.), and Department of Radiology (G.A., N.A.P., N.J.N., N.H.P., K.L.G., R.J.J., R.E.C., B.B.C.), Duke University Medical Center, Box 3808 DUMC, Durham, NC 27710; and Department of Radiology, University of Pennsylvania, Philadelphia, Pa (S.D.M.). Received September 1, 2005; revision requested November 3; revision received January 25, 2006; accepted February 6; final version accepted February 28. S.D.M. supported in part by National Institute for Biomedical Imaging and Bioengineering grants R01-EB-001910 and R33-EB-001543. R.J.J. supported in part by shared instrumentation funding from the National Center for Research Resources of the National Institutes of Health grant S10-RR-15697 and National Cancer Institute grant R01-CA-076006. S.V. supported in part by a Howard Hughes Medical Student Research Training Fellowship grant. Address correspondence to B.B.C. (e-mail: chin0004{at}mc.duke.edu).

Purpose: To determine the feasibility of in vivo localization and quantification of indium 111 (¹¹¹In)-oxine–labeled bone marrow (BM) with high-resolution whole-body helical single photon emission computed tomography (SPECT) in an established murine model of atherosclerosis and vascular repair.

Materials and Methods: The institutional animal care and use committee approved this study. BM from young B6 Rosa 26 Lac Z^+/+ mice was radiolabeled with ¹¹¹In-oxine. On days 1, 4, and 7 after administration of radiolabeled cells, five C57/BL6 apolipoprotein E–deficient mice and five wild-type (WT) control mice were imaged with whole-body high-resolution helical SPECT. Quantification with SPECT was compared with ex vivo analysis by means of gamma counting. Autoradiography and ß-galactosidase staining were used to verify donor cell biodistribution. Linear regression was used to assess the correlation between continuous variables. Two-tailed Student t test was used to compare values between groups, and paired two-tailed t test was used to assess changes within subjects at different time points.

Results: SPECT image contrast was high, with clear visualization of BM, liver, and spleen 7 days after administration of radiolabeled cells. SPECT revealed that 42% and 58% more activity was localized to the aorta and BM (P < .05 for both), respectively, in apolipoprotein E–deficient mice versus WT mice. Furthermore, 28% and 27% less activity was localized to the liver and spleen (P < .05 for both), respectively, in apolipoprotein E–deficient mice versus WT mice. SPECT and organ gamma counts showed good quantitative correlation (r = 0.9). ß-Galactosidase staining and microautoradiography of recipient aortas showed donor cell localization to the intima of visible atherosclerotic plaque but not to unaffected regions of the vessel wall.

Conclusion: High-resolution in vivo helical pinhole SPECT can be used to monitor and quantify early biodistribution of ¹¹¹In-oxine–labeled BM in a murine model of progenitor cell therapy for atherosclerosis.

© RSNA, 2007