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Meeting ReportCardiovascular

Utility of [18F]AS3504073-00, Novel PET Ligand for Fatty-Acid Oxidation, for Cardiac Dysfunction in Monkey and Rodent Model.

Hiroshi Fushiki and Yoshihiro Murakami
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 219;
Hiroshi Fushiki
1Bioimaging Research Astellas Pharma Inc. Tsukuba Japan
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Yoshihiro Murakami
1Bioimaging Research Astellas Pharma Inc. Tsukuba Japan
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Abstract

219

Purpose: Myocardial energy metabolism is mainly dependent on Fatty Acid Oxidation (FAO) in ATP production, however, FAO alteration in cardiac dysfunction is still unclear. We have identified [18F]AS3504073-00 as a novel PET probe for FAO with good property on higher uptake in heart and no defluorination in vivo. To understand the mechanism of the alteration of FAO in cardiac dysfunction, PET imaging examination with [18F]AS3504073-00 was conducted in ischemic heart disease and cardiomyopathy model in monkeys and hamsters.

Methods: [18F]AS3504073-00 and [13N]ammonia were synthesized in house. J2N-k and -n hamster were used as cardiomyopathic model and normal control, respectively. Longitudinal PET imaging with [18F]AS3504073-00 was demonstrated to monitor the FAO status in both animals. Heart infraction model in monkey was established by occluding left anterior descending coronary artery (LAD). Head-to head comparison of PET imaging with [18F]AS3504073-00 and [13N]ammonia in acute (1-week) and subchronic (1-month) phase was conducted in ischemic heart disease monkey models

Results: [18F]AS3504073-00 was successfully synthesized with enough quality and purity. In J2N-k cardiomyopathic hamster model, less uptake of [18F]AS3504073-00 in heart was observed compared to that in J2N-n normal hamster at least 8-week after the birth, when there was no abnormal phenotype on the ejection fraction in both animals. In monkey LAD occlusion model, [18F]AS3504073-00 and [13N]ammonia was visualized ischemic region at acute and subchronic phase. Although the comparable accumulation of [13N] Ammonia was observed in non-ischemic heart region in both phase, the higher uptake of [18F]AS3504073-00 was observed in non-ischemic heart region at subchronic phase rather than that at acute phase. These observations might reflect the metabolic dysfunction and the remodeling in cardiomyophathy and ischemic heart disease, respectively.

Conclusions: [18F]AS3504073-00 is shown to be a potential tool of FAO PET probe. The character of [18F]AS3504073-00 warrants the usefulness with good specificity and imaging efficacious window in clarifying the several heart disease mechanism and region from FAO point of view.

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Journal of Nuclear Medicine
Vol. 61, Issue supplement 1
May 1, 2020
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Utility of [18F]AS3504073-00, Novel PET Ligand for Fatty-Acid Oxidation, for Cardiac Dysfunction in Monkey and Rodent Model.
Hiroshi Fushiki, Yoshihiro Murakami
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 219;

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Utility of [18F]AS3504073-00, Novel PET Ligand for Fatty-Acid Oxidation, for Cardiac Dysfunction in Monkey and Rodent Model.
Hiroshi Fushiki, Yoshihiro Murakami
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 219;
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