Eung Ju Kim1, Sungeun Kim2, Hong Seog Seo3,4, Yong Jik Lee1, Jae Seon Eo2, Jae Min Jeong5, Boeun Lee6, Jae Young Kim7, Young Mi Park8, Myeongsook Jeong8. 1. Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea. 2. Nuclear Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea. 3. Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea mdhsseo@korea.ac.kr jmjng@snu.ac.kr. 4. Korea University-Korea Institute of Science and Technology (KU-KIST) Graduate School of Converging Science and Technology, Seoul, South Korea. 5. Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea mdhsseo@korea.ac.kr jmjng@snu.ac.kr. 6. Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea. 7. Research Institute of Skin Imaging, Korea University College of Medicine, Seoul, South Korea; and. 8. Department of Molecular Medicine, Ewha Womans University School of Medicine, Seoul, South Korea.
Abstract
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.
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 humanserum 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.
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