¹⁴C-Methionine Uptake as a Potential Marker of Inflammatory Processes After Myocardial Ischemia and Reperfusion

Abstract

A relationship between L-[methyl-11 C]methionine ( 11 C-methionine) uptake and angiogenesis has been suggested in gliomas. However, methionine uptake in myocardial ischemia and reperfusion has received little attention. We investigated the serial changes and mechanisms of 14 C-methionine uptake in a rat model of myocardial ischemia and reperfusion. Methods: The left coronary artery was occluded for 30 min, followed by reperfusion for 1-28 d. At the time of the study, 14 C-methionine (0.74 MBq) and 201 Tl (14.8 MBq) were injected intravenously at 20 and 10 min before sacrifice, respectively. One minute before sacrifice, the left coronary artery was reoccluded, and 99m Tc-hexakis-2-methoxyisobutylisonitrile (150-180 MBq) was injected to verify the area at risk. Histologic sections of the heart were immunohistochemically analyzed using anti-CD68, anti-smooth-muscle a-actin (SMA), and antitroponin I and compared with the autoradiography findings. Results: Both 14 Cmethionine (uptake ratio, 0.71 6 0.13) and 201 Tl uptake were reduced in the area at risk at 1 d after reperfusion. However, 3 d after reperfusion, an increased 14 C-methionine uptake (1.79 6 0.23) was observed corresponding to the area of still-reduced 201 Tl uptake, and the 14 C-methionine uptake gradually declined until 28 d. The increased 14 C-methionine uptake area at 3 and 7 d corresponded well to the macrophage infiltrations demonstrated by positive CD68 staining. Anti-SMA staining appeared at 7 d, after which CD68 staining was gradually replaced by the SMA staining, suggesting that methionine uptake in the early phase after ischemia and reperfusion might reflect inflammatory activity. Conclusion: 14 C-methionine accumulated in the infarcted area, and its uptake corresponded closely to macrophage infiltration at 3-7 d after reperfusion. Methionine imaging may be useful for inflammatory imaging early after myocardial infarction.

Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction

“…A preliminary study identified myocardial uptake of 11 C-methionine in acute myocardial infarction patients at up to 2 weeks after coronary reperfusion 12. Moreover, recent ex vivo evidence suggested that methionine may serve as a potential marker of post-infarct inflammation 13.…”

11C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis

“…Recently, several experimental studies have suggested the potential of 11 C-methionine PET to detect inflammatory lesions (16,17). Kubota et al reported that methionine uptake is increased in macrophages that invade tumor lesions (18).…”

Imaging of Post-Infarct Inflammation

“…Further steps may include the evaluation of tracers other than FDG, such as the amino acid methionine 16 or the chemokine-targeted agent pentixafor. 17 In parallel, early inflammation-targeted molecular imaging may be implemented in larger post-AMI outcome registries to bolster the notion of its predictive value.…”