Positron Emission Tomography (PET) with 18 F-FGA for Diagnosis of Myocardial Infarction in a Coronary Artery Ligation Model.

Autor: Awasthi V; College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.; Hexakit, Inc., 505 NE 46th, Oklahoma City, Oklahoma, USA., Gali H; College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA., Hedrick AF; College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA., Da H; College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA., Eeda V; College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA., Jain D; Westchester Medical Center, 100 Woods Road, Valhalla, NY, USA.
Jazyk: angličtina
Zdroj: Molecular imaging [Mol Imaging] 2022 Feb 09; Vol. 2022, pp. 9147379. Date of Electronic Publication: 2022 Feb 09 (Print Publication: 2022).
DOI: 10.1155/2022/9147379
Abstrakt: Location and extent of necrosis are valuable information in the management of myocardial infarction (MI). Methods . We investigated 2-deoxy-2- 18 F-fluoro glucaric acid (FGA), a novel infarct-avid agent, for positron emission tomography (PET) of MI. We synthesized FGA from commercially available 18 F-fluoro-2-deoxy-2-D-glucose (FDG). MI was induced in mice by permanently occluding the left anterior descending coronary artery. Biodistribution of FGA was assessed 1 h after FGA injection (11 MBq). PET/CT was conducted 1 h, 6 h, 1 d, 3 d, and 4 d after MI. Subcellular compartment of FGA accumulation in necrosis was studied by tracing the uptake of biotin-labeled glucaric acid with streptavidin-HRP in H 2 O 2 -treated H9c2 cardiomyoblasts. Streptavidin-reactive protein bands were identified by LC-MS/MS. Results . We obtained a quantitative yield of FGA from FDG within 7 min (radiochemical purity > 99%). Cardiac uptake of FGA was significantly higher in MI mice than that in control mice. Imaging after 1 h of FGA injection delineated MI for 3 days after MI induction, with negligible background signal from surrounding tissues. Myocardial injury was verified by tetrazolium staining and plasma troponin (47.63 pg/mL control versus 311.77 pg/mL MI). In necrotic H9c2 myoblasts, biotinylated glucaric acid accumulated in nuclear fraction. LC-MS/MS primarily identified fibronectin in necrotic cells as a putative high fidelity target of glucaric acid. Conclusion . FGA/PET detects infarct early after onset of MI and FGA accumulation in infarct persists for 3 days. Its retention in necrotic cells appears to be a result of interaction with fibronectin that is known to accumulate in injured cardiac tissue.
Competing Interests: Dr. V. Awasthi owns Hexakit, Inc. that was awarded STTR funding. No other potential conflicts of interest relevant to this article exist.
(Copyright © 2022 Vibhudutta Awasthi et al.)
Databáze: MEDLINE
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