Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligand
Abstract Background Heart-type fatty acid binding proteins (FABP3) constitute a family of lipid chaperone proteins. They are found in the cytosol and enhance cellular fatty acid solubilisation, transport, and metabolism. FABP3 is highly expressed in the myocardium and is released from myocytes durin...
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SpringerOpen
2024-11-01
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| Series: | EJNMMI Research |
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| Online Access: | https://doi.org/10.1186/s13550-024-01175-6 |
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| author | Jun Toyohara Taichi Komoda Tetsuro Tago Masahiko Ito Hiroshi Yoshino |
| author_facet | Jun Toyohara Taichi Komoda Tetsuro Tago Masahiko Ito Hiroshi Yoshino |
| author_sort | Jun Toyohara |
| collection | DOAJ |
| description | Abstract Background Heart-type fatty acid binding proteins (FABP3) constitute a family of lipid chaperone proteins. They are found in the cytosol and enhance cellular fatty acid solubilisation, transport, and metabolism. FABP3 is highly expressed in the myocardium and is released from myocytes during myocardial damage. As FABP3 content in the myocardium is closely related to the metabolic state of fatty acids, we hypothesised that targeting of FABP3 with a radiolabelled small organic compound would visualise myocardium. Results The selective FABP3 inhibitor, 4-(4-fluoro-2-(1-phenyl-5-(2-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)phenoxy)butanoic acid (LUF), was radiolabelled via a two-step reaction comprising copper-mediated 18F-fluorination of an arylboronic precursor followed by alkaline hydrolysis of the ethoxy protecting group. [18F]LUF was successfully synthesised by automated synthesiser with sufficient activity yields (14.0 ± 1.8 GBq) and high quality (molar activity, > 250 GBq/µmol and radiochemical purity, > 99.6%). Biological assessment of [18F]LUF as an in vivo myocardial imaging agent included evaluations of biodistribution, metabolite analysis, and positron emission tomography (PET) imaging of small animals. [18F]LUF clearly visualised the myocardium with high contrast against background tissues such as the lung and liver. [18F]LUF also showed a high absolute myocardial uptake equivalent to that of the promising myocardial perfusion tracer [18F]flurpiridaz and excellent metabolic stability in the body. These properties are ideal for stable and noise-less imaging of the heart. PET imaging of rat surgical permanent myocardial infarction (MI) and experimental autoimmune myocarditis (EAM) was also performed. [18F]LUF successfully visualised lesions of permanent MI and EAM. Conclusion Our results showed for the first time that the 18F-labelled FABP3 selective small organic compound clearly visualised myocardium with good quality. To determine the clinical utility of [18F]LUF for cardiovascular disease in clinical practice, it will be necessary to evaluate a greater variety of cardiovascular disease models and elucidate the accumulation mechanism, particularly in relation to fatty acid metabolism in the myocardium. |
| format | Article |
| id | doaj-art-85d88331ee76494c901325c387fee9a1 |
| institution | Kabale University |
| issn | 2191-219X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | SpringerOpen |
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| series | EJNMMI Research |
| spelling | doaj-art-85d88331ee76494c901325c387fee9a12024-11-17T12:48:27ZengSpringerOpenEJNMMI Research2191-219X2024-11-0114111110.1186/s13550-024-01175-6Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligandJun Toyohara0Taichi Komoda1Tetsuro Tago2Masahiko Ito3Hiroshi Yoshino4Research Team for Neuroimaging, Tokyo Metropolitan Institute for Geriatrics and GerontologyR&D Center, Shiratori Pharmaceuticals Co., Ltd.Research Team for Neuroimaging, Tokyo Metropolitan Institute for Geriatrics and GerontologyR&D Center, Shiratori Pharmaceuticals Co., Ltd.R&D Center, Shiratori Pharmaceuticals Co., Ltd.Abstract Background Heart-type fatty acid binding proteins (FABP3) constitute a family of lipid chaperone proteins. They are found in the cytosol and enhance cellular fatty acid solubilisation, transport, and metabolism. FABP3 is highly expressed in the myocardium and is released from myocytes during myocardial damage. As FABP3 content in the myocardium is closely related to the metabolic state of fatty acids, we hypothesised that targeting of FABP3 with a radiolabelled small organic compound would visualise myocardium. Results The selective FABP3 inhibitor, 4-(4-fluoro-2-(1-phenyl-5-(2-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)phenoxy)butanoic acid (LUF), was radiolabelled via a two-step reaction comprising copper-mediated 18F-fluorination of an arylboronic precursor followed by alkaline hydrolysis of the ethoxy protecting group. [18F]LUF was successfully synthesised by automated synthesiser with sufficient activity yields (14.0 ± 1.8 GBq) and high quality (molar activity, > 250 GBq/µmol and radiochemical purity, > 99.6%). Biological assessment of [18F]LUF as an in vivo myocardial imaging agent included evaluations of biodistribution, metabolite analysis, and positron emission tomography (PET) imaging of small animals. [18F]LUF clearly visualised the myocardium with high contrast against background tissues such as the lung and liver. [18F]LUF also showed a high absolute myocardial uptake equivalent to that of the promising myocardial perfusion tracer [18F]flurpiridaz and excellent metabolic stability in the body. These properties are ideal for stable and noise-less imaging of the heart. PET imaging of rat surgical permanent myocardial infarction (MI) and experimental autoimmune myocarditis (EAM) was also performed. [18F]LUF successfully visualised lesions of permanent MI and EAM. Conclusion Our results showed for the first time that the 18F-labelled FABP3 selective small organic compound clearly visualised myocardium with good quality. To determine the clinical utility of [18F]LUF for cardiovascular disease in clinical practice, it will be necessary to evaluate a greater variety of cardiovascular disease models and elucidate the accumulation mechanism, particularly in relation to fatty acid metabolism in the myocardium.https://doi.org/10.1186/s13550-024-01175-6Fluorine-18Heart-type fatty acid binding protein[18F]LUFMyocardiumPositron emission tomography |
| spellingShingle | Jun Toyohara Taichi Komoda Tetsuro Tago Masahiko Ito Hiroshi Yoshino Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligand EJNMMI Research Fluorine-18 Heart-type fatty acid binding protein [18F]LUF Myocardium Positron emission tomography |
| title | Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligand |
| title_full | Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligand |
| title_fullStr | Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligand |
| title_full_unstemmed | Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligand |
| title_short | Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligand |
| title_sort | light up heart type fatty acid binding protein fabp3 with a novel fluorine 18 labelled selective fabp3 ligand |
| topic | Fluorine-18 Heart-type fatty acid binding protein [18F]LUF Myocardium Positron emission tomography |
| url | https://doi.org/10.1186/s13550-024-01175-6 |
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