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

 Seung-Pyo Lee  ;  Hyung-Jun Im  ;  Shinae Kang  ;  Seock-Jin Chung  ;  Ye Seul Cho  ;  Hyejeong Kang  ;  Ho Seon Park  ;  Do-Won Hwang  ;  Jun-Bean Park  ;  Jin-Chul Paeng  ;  Gi-Jeong Cheon  ;  Yun-Sang Lee  ;  Jae Min Jeong  ;  Yong-Jin Kim 
 THERANOSTICS, Vol.7(2) : 413-424, 2017 
Journal Title
Issue Date
Animals ; Disease Models, Animal ; Gallium Radioisotopes/administration & dosage* ; Heterocyclic Compounds/administration & dosage* ; Myocarditis/diagnostic imaging* ; Positron-Emission Tomography/methods* ; Rats ; Sensitivity and Specificity ; Serum Albumin/administration & dosage* ; Serum Albumin, Human
macrophage ; mannose receptor ; molecular imaging ; myocarditis ; positron emission tomography
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 68Ga-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 68Ga. The efficacy of 68Ga-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. 68Ga-NOTA-MSA uptake was upregulated in organs of macrophage accumulation, such as liver, spleen, bone marrow and myocardium (0.32 (0.31~0.33) for normal versus 1.02 (0.86~1.06) for myocarditis (median (range), SUV); n=4~6 per group, p-value=0.01). 68Ga-NOTA-MSA uptake in the left ventricle was upregulated in myocarditis compared with normal rats (2.29 (1.42~3.40) for normal versus 4.18 (3.43~6.15) 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 (2.59~3.86) for myocarditis versus 2.28 (1.76~2.60) 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. 68Ga-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 68Ga-NOTA-MSA PET in the early diagnosis of as well as in the monitoring of treatment response of myocarditis.
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Yonsei Authors
Kang, Shin Ae(강신애) ORCID logo https://orcid.org/0000-0002-9719-4774
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