Abstract
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Objectives Optimizing the inflammatory response after myocardial infarction is a promising therapeutic target, although further detailed understanding of the underlying biology is still necessary. Longitudinal imaging of the inflammatory activity would be helpful to investigate anti-inflammatory strategies. We studied the potential of 11C-methionine PET for monitoring inflammation after myocardial infarction.
Methods In Wistar rats, myocardial infarction was induced by transient ligation of the left coronary artery for 30 minutes. High-resolution micro-autoradiography was performed to determine tracer accumulation in the microscopic level (n=2). On day 3 after infarction, 14C-methionine (0.74 MBq) was injected via the tail vein. After 20 minutes of tracer distribution, the heart was extracted, frozen and cut into 20-μm short axis slices. The sections were dipped into NTB-2 liquid emulsion (Kodak), exposed for 1 month in the dark, and then developed to visualize exposed silver grains (black dots). CD68 immunohistochemical staining was performed in the adjacent slices. Additionally, on day 3, dynamic cardiac 11C-methionine PET was conducted to evaluate the feasibility of in vivo imaging in rats after transient coronary ligation (n=2) and in healthy controls (n=4). 18F-FDG PET was also performed under insulin and glucose stimulation as a reference.
Results Intense cellular infiltrations of CD68 positive inflammatory cells in the ischemic areas were histologically documented. Light microscopy images of micro-autoradiographic analysis showed a well-matched localization of the black dots (14C-methionine activity) and the CD68 positive cells (% area of black dots in CD68 positive cells and CD68 negative cells = 43.3 ± 14.0 vs 5.0 ± 3.2, P<.0001). In vivo 11C-methionine PET successfully visualized focal tracer uptake in the infarcted areas identified by 18F-FDG PET (Averaged myocardial 11C-methionine activity = 0.47 ± 0.01 %ID/cm3), while no obvious focal 11C-methionine uptake was depicted in the control hearts (0.10 ± 0.01 %ID/cm3).
Conclusions The present animal experiments demonstrate a promising potential of 11C-methionine PET imaging to visualize macrophage infiltration after myocardial infarction.