Evaluation of 18F-labeled BODIPY dye as potential PET agents for myocardial perfusion imaging
Evaluation of 18F-labeled BODIPY dye as potential PET agents for myocardial perfusion imaging
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DOI：
10.1016/j.nucmedbio.2013.09.006
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发表时间：
2014-01-01
影响因子：
3.1
通讯作者：
Conti, Peter S.
中科院分区：
文献类型：
--
作者：
Liu, Shuanglong;Li, Dan;Conti, Peter S.
简介：尽管正电子发射断层扫描/计算机断层扫描（PET/CT）在心血管疾病成像中具有巨大的潜力，但主要限制之一是具有理想半衰期和合理成本的PET探头的可用性。方法：以刘易斯酸氯化锡（SnCl 4）为催化剂，通过氟离子交换反应合成了F-18标记的BODIPY染料（[F-18]1）。结果：[F-18]1的标记率大于90%，放射化学纯度大于98%。HEK-293细胞摄取试验表明，[F-18]1的优先摄取可能与细胞膜电位有关。生物分布数据表明，[F-18]1在心脏中蓄积水平较高。在小鼠生物分布研究中，注射后3 h（p.i.），心脏、血液、肝脏和肺中的放射性摄取分别为3.01 +/- 0.44、0.39 +/- 0.09、0.69 +/- 0.07、1.71 +/- 0.27%ID/g。在注射后3 h，心脏与肺和心脏与肝脏的比值分别为1.76 +/- 0.14和4.37 +/- 0.51，分别microPET图像的感兴趣体积分析与小鼠中的生物分布研究相关性良好。在正常大鼠中心脏清晰可见，在注射后0.5、1、2和4小时具有0.72 +/-0.18、0.69 +/- 0.18、0.67 +/- 0.20和0.59 +/- 0.17%ID/g摄取，结论：F-18标记的BODIPY染料显示出良好的心脏摄取以及心脏与血液和心脏与肺的对比。F-18标记的BODIPY染料可能代表一类新的心肌灌注显像阳离子PET剂。(C)2014 Elsevier Inc. All rights reserved.
Introduction: Despite the great potential of positron emission tomography/computed tomography (PET/CT) in cardiovascular disease imaging, one of the major limitations is the availability of PET probes with desirable half-lives and reasonable cost. In this report, we hypothesized that lipophilic cationic BODIPY dye could be selectively accumulated in cardiac muscle, possibly for the development of novel PET myocardial perfusion imaging (MPI) probes.Methods: A F-18-labeled BODIPY dye ([F-18]1) was synthesized efficiently through a fluoride exchange reaction catalyzed by the Lewis acid tin chloride (SnCl4). The compound was first evaluated by a cellular uptake assay in vitro, followed by biodistribution and microPET imaging studies in vivo.Results: [F-18]1 was obtained in more than 90% labeling yield, with >98% radiochemical purity. The HEK-293 cellular uptake assay showed that the preferential uptake of [F-18]1 could be related to the cell membrane potential. The biodistribution data demonstrated high levels of [F-18]1 accumulation in the heart. In the biodistribution study in mice, the radioactivity uptake in the heart, blood, liver and lung was 3.01 +/- 0.44, 0.39 +/- 0.09, 0.69 +/- 0.07, 1.71 +/- 0.27%ID/g, respectively, at 3 h post-injection (p.i.). The heart-to-lung and heart-to-liver ratios are 1.76 +/- 0.14 and 4.37 +/- 0.51 at 3 h p.i., respectively. Volume-of-interest analysis of the microPET images correlated well with the biodistribution studies in mice. The heart was clearly visualized in normal rats, with 0.72 +/- 0.18, 0.69 +/- 0.18, 0.67 +/- 0.20 and 0.59 +/- 0.17%ID/g uptake at 0.5, 1, 2 and 4 h p.i., respectively.Conclusions: F-18-labeled BODIPY dye showed good heart uptake and heart-to-blood and heart-to-lung contrast. A F-18-labeled BODIPY dyes may represent a new category of cationic PET agents for myocardial perfusion imaging. (C) 2014 Elsevier Inc. All rights reserved.