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

Abstract

Myocarditis represents a major cause of dilated cardiomyopathy and sudden cardiac death in younger adults. Currently, definitive diagnosis of myocarditis requires endomyocardial biopsy, which is highly invasive and has the drawback of variable sensitivity due to inherent sampling error. Therefore, reliable noninvasive methods to detect and monitor cardiac inflammation are clinically relevant. In this study, we explored the potential of radiolabeled methionine to assess myocardial inflammatory activity in a rat model of experimental autoimmune myocarditis (EAM). Autoimmune myocarditis was induced by immunizing Lewis rats twice with porcine cardiac myosin and Freund complete adjuvant. Control animals were treated with adjuvant alone. Dual-tracer autoradiography was performed to assess ¹⁴C-methionine uptake and to compare the distributions of ¹⁴C-methionine versus ¹⁸F-FDG. Hematoxylin and eosin staining and anti-CD68 macrophage staining were performed for histologic analysis. Additionally, cardiac ¹¹C-methionine PET was performed to evaluate the feasibility of in vivo imaging. ¹⁸F-FDG PET was also conducted to compare the in vivo uptake of ¹¹C-methionine and ¹⁸F-FDG. Multiple focal cardiac inflammatory lesions were histologically identified in myosin-immunized rats, whereas no cardiac lesions were observed in the controls. Autoradiographic images clearly showed a high-density accumulation of ¹⁴C-methionine in inflammatory lesions of EAM rats, whereas no significant uptake was observed in the control animals. ¹⁴C-methionine uptake was significantly higher in inflammatory lesions than in remote noninflammatory areas and control rat hearts. The distribution of ¹⁴C-methionine correlated well with that of ¹⁸F-FDG and with macrophage density. The contrast between inflammatory and noninflammatory areas was higher for ¹⁸F-FDG than for ¹⁴C-methionine (3.45 ± 0.68 vs. 2.07 ± 0.21, respectively; P < 0.05). In the PET imaging study, the regional ¹¹C-methionine uptake (percentage injected dose per cubic centimeter) observed in EAM rats was significantly higher than the values obtained for control animals (0.64 ± 0.09 vs. 0.28 ± 0.02, respectively; P < 0.001). A good positive correlation between ¹¹C-methionine and ¹⁸F-FDG uptake was found. In a rat model of autoimmune myocarditis, we demonstrated the colocalization of radiolabeled methionine accumulation with ¹⁸F-FDG uptake in histologically proven inflammatory lesions. These data suggest that ¹¹C-methionine might represent a promising candidate for the noninvasive detection and monitoring of myocarditis.