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. 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 α-actin (SMA), and antitroponin I and compared with the autoradiography findings. Both (14)C-methionine (uptake ratio, 0.71 ± 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 ± 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. (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.