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 11 C-methionine provides further insight into heart-brain inflammation networking. Methods: Male C57BL/6 mice underwent permanent coronary artery ligation followed by 11 C-methionine PET at 3 and 7 d (n 5 3). In subgroups, leukocyte homing was blocked by integrin antibodies (n 5 5). The cellular substrate for PET signal was identified using brain section immunostaining. Results: 11 C-methionine uptake (percentage injected dose/cm 3 ) 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 (r 5 0.47, P , 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. Conclusion: PET imaging with 11 C-methionine specifically identifies an astrocyte component, enabling further dissection of the heart-brain axis in post-MI inflammation.

Cognitive Dysfunction after Heart Disease: A Manifestation of the Heart‐Brain Axis

“…Neutrophils and proinflammatory monocytes display higher rates of methionine uptake, which affects the activation of astrocytes [ 100 ]. In addition, active astrocytes may be neurotoxic and produce specific inflammatory cytokines and ROS [ 75 ].…”

“…The inflammatory response and oxidative stress mainly cause cognitive dysfunction through damage to the selfrepair mechanism, destruction of the blood-brain barrier (BBB), and activation of glial cells [61,73,74]. Among them, the damaged BBB and activated glial cells will also affect each other, leading to deposition of amyloid-β (Aβ) and causing damage to the cognitive function of the brain [75][76][77].…”

“…After inflammation occurs, astrocytes are activated slightly earlier than microglia [63]. The activation of astrocytes after MI is directly related to the inflammation induced by infarction, and may be caused by proinflammatory cytokines [75]. 11 C-methionine uptake can help reflect inflammation in the brain [99].…”

“…Oxidative Medicine and Cellular Longevity [100]. In addition, active astrocytes may be neurotoxic and produce specific inflammatory cytokines and ROS [75].…”

Imaging Inflammation with Positron Emission Tomography

“…However, methionine uptake is also increased in immune cells such as monocytes/macrophages, B and T cells [ 137 ]. In inflammation, 11 C-methionine has mainly been used to image cardiac inflammation [ 80 , 138 , 139 , 140 ]. Another PET radiotracer that has mostly been evaluated in cancer imaging but also holds promise in imaging inflammation is 3′-deoxy-3′-18F-fluorothymidine (FLT) [ 141 ].…”