Abstract 17159: Targeting Acute Post-Infarct Inflammation with 11C-Methioinine or 18F-Deoxyglucose Positron Emission Tomography in Mice
Inflammation of the tissue microenvironment after myocardial infarction (MI) influences subsequent healing/remodeling and has emerged as a target for molecular therapy and imaging. 18F-Deoxyglucose (FDG) accumulates in activated macrophages but is complicated by robust cardiomyocyte uptake. 11C-Methionine (MET), a marker of de novo protein synthesis, has been proposed as an alternative marker of inflammation. C57Bl/6 mice underwent coronary artery ligation (n=16) or no surgery (n=5). Serial positron emission tomography (PET) images at 3, 5, and 7d post-MI were acquired with either FDG (60 min dynamic, ketamine-xylazine KX suppression) or MET (30 min dynamic). Perfusion was evaluated by 13N-ammonia PET or 99mTc-sestamibi SPECT on d7. Autoradiography was conducted with alternate slices allocated for histopathology. At 7d post-MI, 32-45% of LV exhibited a perfusion defect (<60% max). FDG uptake in MI mice under KX was elevated compared to healthy controls in the infarct and remote myocardial regions (%ID/g, inf 6.3±1.5 v 2.6±0.6; rem 9.6±3.9 v 2.9±0.7, p<0.01). MET infarct uptake was higher compared to remote myocardium and to healthy controls (d3 5.9±0.9 v 4.7±0.9, p=0.08; d5 5.4±0.7 v 4.1±0.7, p=0.04; d7 4.3±0.6 v 3.4±0.8, p=0.10; ctl 2.6, p<0.05). MET accumulation in both infarct and remote territory significantly declined from d3 to d7 post-MI (p<0.01). Autoradiography confirmed both FDG and MET uptake in the infarct territory associated with CD68+ macrophage and Ly6G+ monocyte immunostaining. Following MI, both FDG under KX suppression and MET exhibit increased uptake within the LV infarct territory, consistent with the temporal and spatial pattern of inflammatory cell infiltration post-MI. MET exhibits a lower remote myocardial signal than is observed with FDG. The absence of MET uptake by healthy myocytes and lower accumulation in remote myocardium post-MI suggest that MET may be a viable alternative for molecular imaging of early post-MI inflammation.
Author Disclosures: J.T. Thackeray: None. Y. Wang: None. J.P. Bankstahl: None. K.C. Wollert: None. F.M. Bengel: None.
- © 2014 by American Heart Association, Inc.