Molecular Imaging of Diffuse Cardiac Fibrosis with a Radiotracer That Targets Proteolyzed Collagen IV.

IF 3.8 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Be'eri Niego, Bianca Jupp, Nicholas A Zia, Rong Xu, Edwina Jap, Martin Ezeani, Asif Noor, Paul S Donnelly, Christoph E Hagemeyer, Karen Alt
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Abstract

Purpose To develop an approach for in vivo detection of interstitial cardiac fibrosis using PET with a peptide tracer targeting proteolyzed collagen IV (T-peptide). Materials and Methods T-peptide was conjugated to the copper chelator MeCOSar (chemical name, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid) and radiolabeled with copper 64 (64Cu). PET/CT scans were acquired following intravenous delivery of 64Cu-T-peptide-MeCOSar (0.25 mg/kg; 18 MBq ± 2.7 [SD]) to male transgenic mice overexpressing β2-adrenergic receptors with intermediate (7 months of age; n = 4 per group) to severe (10 months of age; n = 11 per group) cardiac fibrosis and their wild-type controls. PET scans were also performed following coadministration of the radiolabeled probe with nonlabeled T-peptide in excess to confirm binding specificity. PET data were analyzed by t tests for static scans and analysis of variance tests (one- or two-way) for dynamic scans. Results PET/CT scans revealed significantly elevated (2.24-4.26-fold; P < .05) 64Cu-T-peptide-MeCOSar binding in the fibrotic hearts of aged transgenic β2-adrenergic receptor mice across the entire 45-minute acquisition period compared with healthy controls. The cardiac tracer accumulation and presence of diffuse cardiac fibrosis in older animals were confirmed by gamma counting (P < .05) and histologic evaluation, respectively. Coadministration of a nonradiolabeled probe in excess abolished the elevated radiotracer binding in the aged transgenic hearts. Importantly, PET tracer accumulation was also detected in younger (7 months of age) transgenic mice with intermediate cardiac fibrosis, although this was only apparent from 20 minutes following injection (1.6-2.2-fold binding increase; P < .05). Conclusion The T-peptide PET tracer targeting proteolyzed collagen IV provided a sensitive and specific approach of detecting diffuse cardiac fibrosis at varying degrees of severity in a transgenic mouse model. Keywords: Diffuse Cardiac Fibrosis, Molecular Peptide Probe, Molecular Imaging, PET/CT © RSNA, 2024.

利用针对蛋白水解胶原 IV 的放射性示踪剂对弥漫性心脏纤维化进行分子成像。
目的 开发一种利用正电子发射计算机断层显像技术(PET)检测体内心脏间质纤维化的方法,该方法使用的多肽示踪剂靶向蛋白水解胶原 IV(T-肽)。材料与方法 将 T 肽与铜螯合剂 MeCOSar(化学名称:5-(8-甲基-3,6,10,13,16,19-六氮杂双环[6.6.6]伊可新-1-氨基)-5-氧代戊酸)共轭,并用铜 64 (64Cu) 进行放射性标记。在静脉注射 64Cu-T-peptide-MeCOSar (0.25 mg/kg; 18 MBq ± 2.7 [SD])给中度(7 个月大;每组 n = 4)至重度(10 个月大;每组 n = 11)心脏纤维化的过表达 β2-肾上腺素能受体雄性转基因小鼠及其野生型对照组后,进行 PET/CT 扫描。为了确认结合的特异性,还在放射性标记探针与过量的非标记T肽共同给药后进行了PET扫描。静态扫描的 PET 数据采用 t 检验,动态扫描的 PET 数据采用方差分析检验(单因素或双因素)。结果 PET/CT 扫描显示,与健康对照组相比,在整个 45 分钟的采集期间,老龄转基因 β2-肾上腺素能受体小鼠纤维化心脏中的 64Cu-T 肽-MeCOSar 结合率明显升高(2.24-4.26 倍;P < .05)。伽马计数(P < .05)和组织学评估分别证实了老年动物的心脏示踪剂积累和弥漫性心脏纤维化的存在。同时过量使用非放射性标记探针可消除老年转基因心脏中升高的放射性示踪剂结合。重要的是,在较年轻(7 个月大)的中度心脏纤维化转基因小鼠中也检测到了 PET 示踪剂的积累,尽管这只在注射后 20 分钟才显现出来(结合增加 1.6-2.2 倍;P < .05)。结论 以蛋白水解胶原 IV 为靶点的 T 肽 PET 示踪剂为检测转基因小鼠模型中不同严重程度的弥漫性心脏纤维化提供了一种灵敏而特异的方法。关键词:弥漫性心脏纤维化弥漫性心脏纤维化 分子肽探针 分子成像 PET/CT © RSNA, 2024.
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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