Novel PET imaging of atherosclerosis with 68Ga-Labeled NOTA-Neomannosylated human serum albumin

Eung Ju Kim, Sungeun Kim, Hong Seog Seo, Yong Jik Lee, Jae Seon Eo, Jae Min Jeong, Boeun Lee, Jae Young Kim, Young Mi Park, Myeongsook Jeong

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1792-1797
Number of pages6
JournalJournal of Nuclear Medicine
Volume57
Issue number11
DOIs
Publication statusPublished - 2016 Nov 1

Fingerprint

Serum Albumin
Atherosclerosis
Fluorodeoxyglucose F18
Atherosclerotic Plaques
Macrophages
Aorta
Blocking Antibodies
1,4,7-triazacyclononane-N,N',N''-triacetic acid
Glucose
Facilitative Glucose Transport Proteins
Radiopharmaceuticals
Inferior Vena Cava
Peritoneal Macrophages
Fluorescein
Confocal Microscopy
Neuroimaging
Flow Cytometry
Arteries
Fluorescence
Cholesterol

Keywords

  • Atherosclerosis
  • Inflammation
  • Mannose receptor
  • Positron emission tomography

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Novel PET imaging of atherosclerosis with 68Ga-Labeled NOTA-Neomannosylated human serum albumin. / Kim, Eung Ju; Kim, Sungeun; Seo, Hong Seog; Lee, Yong Jik; Eo, Jae Seon; Jeong, Jae Min; Lee, Boeun; Kim, Jae Young; Park, Young Mi; Jeong, Myeongsook.

In: Journal of Nuclear Medicine, Vol. 57, No. 11, 01.11.2016, p. 1792-1797.

Research output: Contribution to journalArticle

Kim, Eung Ju ; Kim, Sungeun ; Seo, Hong Seog ; Lee, Yong Jik ; Eo, Jae Seon ; Jeong, Jae Min ; Lee, Boeun ; Kim, Jae Young ; Park, Young Mi ; Jeong, Myeongsook. / Novel PET imaging of atherosclerosis with 68Ga-Labeled NOTA-Neomannosylated human serum albumin. In: Journal of Nuclear Medicine. 2016 ; Vol. 57, No. 11. pp. 1792-1797.
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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.",
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AU - Eo, Jae Seon

AU - Jeong, Jae Min

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