¹¹C-Methionine PET Identifies Astroglia Involvement in Heart–Brain Inflammation Networking After Acute Myocardial Infarction

Abstract

Acute myocardial infarction (MI) triggers a local and systemic inflammatory response. We recently showed microglia involvement using translocator protein imaging. Here, we evaluated whether ¹¹C-methionine provides further insight into heart-brain inflammation networking. <b>Methods:</b> Male C57BL/6 mice underwent permanent coronary artery ligation followed by ¹¹C-methionine PET at 3 and 7 d (<i>n</i> = 3). In subgroups, leukocyte homing was blocked by integrin antibodies (<i>n</i> = 5). The cellular substrate for PET signal was identified using brain section immunostaining. <b>Results:</b>¹¹C-methionine uptake (percentage injected dose/cm³) peaked in the MI region on day 3 (5.9 ± 0.9 vs. 2.4 ± 0.5), decreasing to the control level by day 7 (4.3 ± 0.6). Brain uptake was proportional to cardiac uptake (<i>r</i> = 0.47, <i>P</i> < 0.05), peaking also on day 3 (2.9 ± 0.4 vs. 2.4 ± 0.3) and returning to baseline on day 7 (2.3 ± 0.4). Integrin blockade reduced uptake at every time point. Immunostaining on day 3 revealed colocalization of the l-type amino acid transporter, with glial fibrillary acidic protein-positive astrocytes but not CD68-positive microglia. <b>Conclusion:</b> PET imaging with ¹¹C-methionine specifically identifies an astrocyte component, enabling further dissection of the heart-brain axis in post-MI inflammation.