1. Development, synthesis, and 68 Ga-Labeling of a Lipophilic complexing agent for atherosclerosis PET imaging.
- Author
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Yong-Sang J, Dioury F, Meneyrol V, Ait-Arsa I, Idoumbin JP, Guibbal F, Patché J, Gimié F, Khantalin I, Couprie J, Giraud P, Benard S, Ferroud C, Jestin E, and Meilhac O
- Subjects
- Animals, Aorta metabolism, Aorta pathology, Apolipoproteins E genetics, Carotid Arteries metabolism, Carotid Arteries pathology, Chelating Agents chemical synthesis, Drug Carriers chemistry, Drug Development, Heterocyclic Compounds, 2-Ring chemical synthesis, Humans, Lipoproteins, HDL chemistry, Liver metabolism, Mice, Knockout, Myocardium metabolism, Myocardium pathology, Phosphatidylethanolamines chemical synthesis, Positron-Emission Tomography methods, Radiopharmaceuticals chemical synthesis, Atherosclerosis diagnostic imaging, Chelating Agents chemistry, Gallium Radioisotopes chemistry, Heterocyclic Compounds, 2-Ring chemistry, Phosphatidylethanolamines chemistry, Radiopharmaceuticals chemistry
- Abstract
Cardiovascular disease is the leading cause of mortality and morbidity worldwide. Atherosclerosis accounts for 50% of deaths in western countries. This multifactorial pathology is characterized by the accumulation of lipids and inflammatory cells within the vascular wall, leading to plaque formation. We describe herein the synthesis of a PCTA-based
68 Ga3+ chelator coupled to a phospholipid biovector 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), which is the main constituent of the phospholipid moiety of High-Density Lipoprotein (HDL) phospholipid moiety. The resulting68 Ga-PCTA-DSPE inserted into HDL particles was compared to18 F-FDG as a PET agent to visualize atherosclerotic plaques. Our agent markedly accumulated within mouse atheromatous aortas and more interestingly in human endarterectomy carotid samples. These results support the potential use of68 Ga-PCTA-DSPE-HDL for atherosclerosis PET imaging., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)- Published
- 2019
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