Targeting amino acid metabolism for molecular imaging of inflammation early after myocardial infarction

James T. Thackeray, Jens P. Bankstahl, Yong Wang, Kai C. Wollert, Frank M. Bengel

Research output: Contribution to journalArticle

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 11C-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 11C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher 11C-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 11C-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 11C-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 11C-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 11C-methionine uptake by 46% at 3d post-MI. A patient study at 3d after ST-elevation MI and early reperfusion confirmed elevated 11C-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. 11C-methionine-based molecular imaging may assist in the translation of novel image-guided, inflammation-targeted regenerative therapies.

Original languageEnglish (US)
Pages (from-to)1768-1779
Number of pages12
JournalTheranostics
Volume6
Issue number11
DOIs
StatePublished - 2016

Keywords

  • C-methionine
  • Inflammation
  • Macrophages
  • Myocardial infarction
  • Positron emission tomography (PET)

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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  • Cite this

    Thackeray, J. T., Bankstahl, J. P., Wang, Y., Wollert, K. C., & Bengel, F. M. (2016). Targeting amino acid metabolism for molecular imaging of inflammation early after myocardial infarction. Theranostics, 6(11), 1768-1779. https://doi.org/10.7150/thno.15929