한빛사 논문
Jun-Bean Park1,2, Minseok Suh3, Ji Yong Park3, Jin Kyun Park4, Yong-il Kim5, Hyunah Kim1, Ye Seul Cho1, Hyejeong Kang1, Kibyung Kim6, Jae-Hoon Choi6, Jin-Wu Nam6, Hyung-Kwan Kim1,2, Yun-Sang Lee3, Jae Min Jeong3, Yong-Jin Kim1,2, Jin Chul Paeng3,*, and Seung-Pyo Lee1,2,*
1 Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea; 2 Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 3 Department of Nuclear Medicine and 4 Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Republic of Korea; 5 Department of Nuclear Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea; and 6 Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of Korea
Correspondence and requests for reprints should be addressed to Seung-Pyo Lee, M.D., Ph.D., Cardiovascular Center, Seoul National University Hospital, and Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongro-gu, Seoul 03080, Korea.
*These authors jointly supervised the work as co–senior authors.
Abstract
Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.
Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).
Methods: We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and 68Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of 68Ga-NOTA-MSA PET was explored in patients with PAH.
Measurements and Main Results: Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of 68Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of 68Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of 68Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (P = 0.009) or than those with pulmonary hypertension by left heart disease (P = 0.019) (n = 5 per group).
Conclusions: 68Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that 68Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.
Keywords: pulmonary artery hypertension; molecular imaging; macrophage; diagnosis; monitoring
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