Assessment of Inflammation in Pulmonary Artery Hypertension by 68Ga-Mannosylated Human Serum Albumin
- Authors
- Park, Jun-Bean; Suh, Minseok; Park, Ji Yong; Park, Jin Kyun; Kim, Yong-il; Kim, Hyunah; Cho, Ye Seul; Kang, Hyejeong; Kim, Kibyung; Choi, Jae-Hoon; Nam, Jin-Wu; Kim, Hyung-Kwan; Lee, Yun-Sang; Jeong, Jae Min; Kim, Yong-Jin; Paeng, Jin Chul; Lee, Seung-Pyo
- Issue Date
- Jan-2020
- Publisher
- AMER THORACIC SOC
- Keywords
- pulmonary artery hypertension; molecular imaging; macrophage; diagnosis; monitoring
- Citation
- AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, v.201, no.1, pp.95 - 106
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
- Volume
- 201
- Number
- 1
- Start Page
- 95
- End Page
- 106
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/11428
- DOI
- 10.1164/rccm.201903-0639OC
- ISSN
- 1073-449X
- 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, Ga-68-2-(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 Ga-68-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of Ga-68-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 Ga-68-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 Ga-68-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of Ga-68-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: Ga-68-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 Ga-68-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.
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