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- Title
Assessment of Inflammation in Pulmonary Artery Hypertension by <sup>68</sup>Ga-Mannosylated Human Serum Albumin.
- Authors
Jun-Bean Park; Minseok Suh; Ji Yong Park; Jin Kyun Park; Yong-il Kim; Hyunah Kim; Ye Seul Cho; Hyejeong Kang; Kibyung Kim; Jae-Hoon Choi; Jin-Wu Nam; Hyung-Kwan Kim; Yun-Sang Lee; Jae Min Jeong; Yong-Jin Kim; Jin Chul Paeng; Seung-Pyo Lee; Park, Jun-Bean; Suh, Minseok; Park, Ji Yong
- 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.
- Subjects
INFLAMMATION; PULMONARY artery; HYPERTENSION; ALBUMINS; MACROPHAGES
- Publication
American Journal of Respiratory & Critical Care Medicine, 2020, Vol 201, Issue 1, p95
- ISSN
1073-449X
- Publication type
journal article
- DOI
10.1164/rccm.201903-0639OC