title: Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction.
abstract: Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. Molecular imaging holds promise for guidance of such therapies. The amino acid (11)C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with (11)C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher (11)C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (p<0.001). C57Bl/6 mice (n=27) underwent coronary artery ligation or no surgery. Serial (11)C-methionine PET was performed 3, 5 and 7d later. MI mice exhibited a perfusion defect in 32-50% of the left ventricle (LV). PET detected increased (11)C-methionine accumulation in the infarct territory at 3d (5.9±0.9%ID/g vs 4.7±0.9 in remote myocardium, and 2.6±0.5 in healthy mice; p<0.05 and <0.01 respectively), which declined by d7 post-MI (4.3±0.6 in infarct, 3.4±0.8 in remote; p=0.03 vs 3d, p=0.08 vs healthy). Increased (11)C-methionine uptake was associated with macrophage infiltration of damaged myocardium. Treatment with anti-integrin antibodies (anti-CD11a, -CD11b, -CD49d; 100µg) lowered macrophage content by 56% and (11)C-methionine uptake by 46% at 3d post-MI. A patient study at 3d after ST-elevation MI and early reperfusion confirmed elevated (11)C-methionine uptake in the hypoperfused myocardial region. Targeting of elevated amino acid metabolism in pro-inflammatory M1 macrophages enables PET imaging-derived demarcation of tissue inflammation after MI. (11)C-methionine-based molecular imaging may assist in the translation of novel image-guided, inflammation-targeted regenerative therapies.
authors: 1. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany;
authors: James T
authors: JT
authors: Thackeray
authors: 1. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany;
authors: Jens P
authors: JP
authors: Bankstahl
authors: 2. Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors: Yong
authors: Y
authors: Wang
authors: 2. Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors: Kai C
authors: KC
authors: Wollert
authors: 1. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany;
authors: Frank M
authors: FM
authors: Bengel
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000032:analysis*; D004195:Disease Models, Animal; D007249:Inflammation / Q000000981:diagnostic imaging* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008715:Methionine / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D002247:Carbon Isotopes; D008715:Methionine
keywords: 11C-methionine; inflammation; macrophages; myocardial infarction; positron emission tomography (PET).