Noninvasive Imaging of Myocardial Inflammation in Myocarditis using Ga-68-tagged Mannosylated Human Serum Albumin Positron Emission Tomography

作者：Lee Seung Pyo; Im Hyung Jun; Kang Shinae; Chung Seock Jin; Cho Ye Seul; Kang Hyejeong; Park Ho Seon; Hwang Do Won; Park Jun Bean; Paeng Jin Chul; Cheon Gi Jeong; Lee Yun Sang; Jeong Jae Min; Kim Yong Jin

来源：Theranostics, 2017, 7(2): 413-424.

DOI：10.7150/thno.15712

• myocarditis
• macrophage
• mannose receptor
• positron emission tomography
• molecular imaging

The diagnosis of myocarditis traditionally relies on invasive endomyocardial biopsy but none of the imaging studies so far are specific for infiltration of the inflammatory cells itself. We synthesized Ga-68-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA) by conjugating human serum albumin with mannose, followed by conjugation with NOTA and labeling it with Ga-68. The efficacy of Ga-68-NOTA-MSA positron emission tomography (PET) for imaging myocardial inflammation was tested in a rat myocarditis model. A significant number of mannose receptor-positive inflammatory cells infiltrated the myocardium in both human and rat myocarditis tissue. Ga-68-NOTA-MSA uptake was upregulated in organs of macrophage accumulation, such as liver, spleen, bone marrow and myocardium (0.32 (0.31 similar to 0.33) for normal versus 1.02 (0.86 similar to 1.06) for myocarditis (median (range), SUV); n=4 similar to 6 per group, p-value=0.01). Ga-68-NOTA-MSA uptake in the left ventricle was upregulated in myocarditis compared with normal rats (2.29 (1.42 similar to 3.40) for normal versus 4.18 (3.43 similar to 6.15) for myocarditis (median (range), average standard uptake value ratio against paraspinal muscle); n=6 per group, p-value < 0.01), which was downregulated in rats with cyclosporine-A treated myocarditis (3.69 (2.59 similar to 3.86) for myocarditis versus 2.28 (1.76 similar to 2.60) for cyclosporine-A treated myocarditis; n=6 per group, p-value < 0.01). The specificity of the tracer was verified by administration of excess non-labeled MSA. Ga-68-NOTA-MSA uptake was significantly enhanced earlier in the evolution of myocarditis before any signs of inflammation could be seen on echocardiography. These results demonstrate the potential utility of visualizing infiltration of mannose receptor-positive macrophages with Ga-68-NOTA-MSA PET in the early diagnosis of as well as in the monitoring of treatment response of myocarditis.

• 出版日期2017