Selective Imaging of Lung Macrophages Using [11C]PBR28-Based Positron Emission Tomography
Selective Imaging of Lung Macrophages Using [11C]PBR28-Based Positron Emission Tomography
复制标题
基于[11C]PBR28的正电子发射断层扫描对肺大血管的选择性成像
DOI：
10.1007/s11307-021-01617-w
复制
发表时间：
2021-06-16
影响因子：
3.1
通讯作者：
Holtzman, Michael J.
中科院分区：
文献类型：
--
作者：
Chen, Delphine L.;Agapov, Eugene;Holtzman, Michael J.
在小鼠肺炎症模型中，我们检测了转运蛋白（TSPO）靶向的正电子发射断层扫描（PET）示踪剂n -乙酰基- n -（2-[C-11]甲氧基苄基）-2-苯氧基-5-吡啶胺（[C-11]PBR28）是否比2-脱氧-2-[F-18]氟-d -葡萄糖（[F-18]FDG）更能区分巨噬细胞显性和中性粒细胞炎症，并评估了小鼠模型和慢性阻塞性肺疾病（COPD）患者肺组织中TSPO与巨噬细胞的关联。在仙台病毒（SeV）感染后49天、巨噬细胞显性炎症期间，以及在SeV感染后3天或中性粒细胞炎症期间内毒素注入后24小时，对野生型（Wt） C57BL/6J或杂合转基因单核细胞缺陷Wt/opT小鼠的肺摄取[C-11]PBR28和[F-18]FDG进行微pet成像量化。小鼠肺切片用Mac3和Ly6G进行细胞鉴定，人肺切片用CD68和中性粒细胞弹性蛋白酶（NE）进行免疫组化染色，检测巨噬细胞和中性粒细胞中的TSPO。在sev感染、内毒素处理和未感染/未处理的对照小鼠中，示踪剂摄取的差异，以及在人肺切片中TSPO染色的中性粒细胞和巨噬细胞群体之间的差异，采用方差分析进行了测试。结果Wt小鼠在SeV感染后49天（D49）巨噬细胞显性炎症中，[C-11]PBR28摄取（注射剂量/ml肺组织百分比）与对照组相比显著增加(p =
Purpose We tested whether the translocator protein (TSPO)-targeted positron emission tomography (PET) tracer, N-acetyl-N-(2-[C-11]methoxybenzyl)-2-phenoxy-5-pyridinamine ([C-11]PBR28), could distinguish macrophage dominant from neutrophilic inflammation better than 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) in mouse models of lung inflammation and assessed TSPO association with macrophages in lung tissue from the mouse models and in patients with chronic obstructive pulmonary disease (COPD). Procedures MicroPET imaging quantified [C-11]PBR28 and [F-18]FDG lung uptake in wild-type (Wt) C57BL/6J or heterozygous transgenic monocyte-deficient Wt/opT mice at 49 days after Sendai virus (SeV) infection, during macrophage-dominant inflammation, and in Wt mice at 3 days after SeV infection or 24 h after endotoxin instillation during neutrophilic inflammation. Immunohistochemical staining for TSPO in macrophages and neutrophils was performed using Mac3 and Ly6G for cell identification in mouse lung sections and CD68 and neutrophil elastase (NE) in human lung sections taken from explanted lungs from patients with COPD undergoing lung transplantation and donor lungs rejected for transplantation. Differences in tracer uptake among SeV-infected, endotoxin-treated, and uninfected/untreated control mice and in TSPO staining between neutrophils and macrophage populations in human lung sections were tested using analysis of variance. Results In Wt mice, [C-11]PBR28 uptake (% injected dose/ml lung tissue) increased significantly with macrophage-dominant inflammation at 49 days (D49) after SeV infection compared to controls (p =