Activated macrophages take up 18F-FDG via glucose transporters, so this compound is useful for atherosclerosis imaging by PET. However, 18F-FDG application is limited for imaging of the heart and brain, in which glucose uptake is high, and in patients with aberrant glucose metabolism. The aims of this study were to confirm that mannosylated human serum albumin (MSA) specifically binds to the mannose receptor (MR) on macrophages and to test the feasibility of 68Ga-labeled NOTA-MSA for PET imaging of atherosclerotic plaques. Methods: The peritoneal macrophages of C57/B6 mice were collected, incubated with rhodamine B isothiocyanate-MSA (10 μg/mL), and evaluated by confocal microscopy and flow cytometry. The same evaluations were performed after preincubation of the macrophages with anti-CD206 MR blocking antibodies. NOTA-MSA was synthesized by conjugating 2-(p-isothiocyanatobenzyl)-1,4,7-Triazacyclononane-1,4,7-Triacetic acid to MSA, followed by labeling with 68Ga. Rabbits with atherosclerotic aorta induced by a 3-mo cholesterol diet and chronic inflammation underwent consecutive PET/CT with 18F-FDG and 68Ga-NOTA-MSA at 2-d intervals. Results: The binding of MSA to MR and its dose-dependent reduction by preincubation with anti- CD206 MR blocking antibody were confirmed. Rhodamine B isothiocyanate and fluorescein isothiocyanate fluorescence colocalized at the atherosclerotic plaque. The 68Ga-NOTA-MSA SUVs of the atherosclerotic aorta were significantly higher than those of the healthy arteries and inferior vena cava and were comparable to those obtained with 18F-FDG. Conclusion: These findings suggest that MR-specific 68Ga-NOTA-MSA is effective for detecting atherosclerosis in the aorta and is a promising radiopharmaceutical for imaging atherosclerosis because of the presence of M2 macrophages in atherosclerotic plaques.
Bibliographical noteFunding Information:
The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked advertisement in accordance with 18 USC section 1734. This study was partly supported by grants from the Korea Institute of Science and Technology Institutional Program (project no. 2E24080); Korea University-Korea Institute of Science and Technology (KU-KIST) Graduate School of Converging Science and Technology (R1307922); and the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C3093). No other potential conflict of interest relevant to this article was reported
© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
- Mannose receptor
- Positron emission tomography