indium-oxine and Atherosclerosis

Monocytes play a key role in atherogenesis, but their participation has been discerned largely via ex vivo analyses of atherosclerotic lesions. We sought to establish a noninvasive technique to determine monocyte trafficking to atherosclerotic lesions in live animals.. Using a micro-single-photon emission computed tomography small-animal imaging system and a Food and Drug Administration-approved radiotracer ([indium 111] oxyquinoline, (111)In-oxine), we demonstrate here that monocyte recruitment to atherosclerotic lesions can be visualized in a noninvasive, dynamic, and 3-dimensional fashion in live animals. We show in vivo that monocytes are recruited avidly to plaques within days of adoptive transfer. Using micro-single-photon emission computed tomography imaging as a screening tool, we were able to investigate modulatory effects on monocyte recruitment in live animals. We found that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors rapidly and substantially reduce monocyte recruitment to existing atherosclerotic lesions, as imaged here in vivo.. This novel approach to track monocytes to atherosclerotic plaques in vivo should have broad applications and create new insights into the pathogenesis of atherosclerosis and other inflammatory diseases.

Topics: Adoptive Transfer; Animals; Apolipoproteins E; Atherosclerosis; Chemotaxis, Leukocyte; Green Fluorescent Proteins; Mice; Mice, Knockout; Mice, Transgenic; Monocytes; Organometallic Compounds; Oxyquinoline; Tomography, Emission-Computed, Single-Photon

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.. 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 beta-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.. 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). beta-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.. 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.

Topics: Animals; Atherosclerosis; Bone Marrow Cells; Bone Marrow Transplantation; Disease Models, Animal; Feasibility Studies; Image Enhancement; Mice; Mice, Inbred C57BL; Mice, Knockout; Organometallic Compounds; Oxyquinoline; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon