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). Methods: 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 14 C-methionine uptake and to compare the distributions of 14 C-methionine versus 18 F-FDG. Hematoxylin and eosin staining and anti-CD68 macrophage staining were performed for histologic analysis. Additionally, cardiac 11 C-methionine PET was performed to evaluate the feasibility of in vivo imaging. 18 F-FDG PET was also conducted to compare the in vivo uptake of 11 C-methionine and 18 F-FDG. Results: 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 14 C-methionine in inflammatory lesions of EAM rats, whereas no significant uptake was observed in the control animals. 14 C-methionine uptake was significantly higher in inflammatory lesions than in remote noninflammatory areas and control rat hearts. The distribution of 14 C-methionine correlated well with that of 18 F-FDG and with macrophage density. The contrast between inflammatory and noninflammatory areas was higher for 18 F-FDG than for 14 C-methionine (3.45 ± 0.68 vs. 2.07 ± 0.21, respectively; P , 0.05). In the PET imaging study, the regional 11 C-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 11 C-methionine and 18 F-FDG uptake was found. Conclusion: In a rat model of autoimmune myocarditis, we demonstrated the colocalization of radiolabeled methionine accumulation with 18 F-FDG uptake in histologically proven inflammatory lesions. These data suggest that 11 C-methionine might represent a promising candidate for the noninvasive detection and monitoring of myocarditis.

Myocardial Inflammation, Measured Using 18‐Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography, Is Associated With Disease Activity in Rheumatoid Arthritis

“…Among the study's limitations, we assumed that FDG uptake corresponded to myocardial inflammation, as was previously shown in other studies , but, for ethical reasons, we could not verify this pathologically in this asymptomatic cohort. An additional limitation is that our final multivariable model accounted for only 10% of the variability in the SUV mean , inviting a search for other possible contributory variables.…”

“…Inflammatory cells are metabolically active and avidly take up FDG via glucose transporters. Moreover, areas of myocardial FDG uptake strongly correlate with the numbers of infiltrating macrophages and T cells on histologic assessment . In the current study, we assessed myocardial FDG uptake among RA patients with no known history of CVD.…”

Novel Noninvasive Nuclear Medicine Imaging Techniques for Cardiac Inflammation

“…Methionine accumulation co-localized with histologically confirmed cardiac inflammatory lesions and [ 18 F]-FDG-uptake, indicating that [ 11 C]-methionine-PET might represent a promising imaging agent for the noninvasive diagnosis of myocarditis (Fig. 4; [92]). Another new approach needing further evaluation includes targeting of somatostatin receptor 2 and has yielded encouraging results in a clinical pilot study [20].…”

Impact of Novel Antidepressants on Cardiac 123I-Metaiodobenzylguanidine Uptake: Experimental Studies on SK-N-SH Cells and Healthy Rabbits

“…3 H-labeled norepinephrine hydrochloride ( 3 Hnorepinephrine) was purchased from Perkin-Elmer. 18 F-FDG was produced as previously described (20).…”