Poly(ADP-ribose) polymerase (PARP)-targeted PET imaging in non-oncology application: a pilot study in preclinical models of nonalcoholic steatohepatitis.

IF 2 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING American journal of nuclear medicine and molecular imaging Pub Date : 2024-02-20 eCollection Date: 2024-01-01
Troels E Jeppesen, Tuo Shao, Jiahui Chen, Jimmy S Patel, Xin Zhou, Andreas Kjaer, Steven H Liang
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Abstract

Poly(ADP-ribose) polymerase (PARP) activation often indicates a disruptive signal to lipid metabolism, the physiological alteration of which may be implicated in the development of non-alcoholic fatty liver disease. The objective of this study was to evaluate the capability of [68Ga]DOTA-PARPi PET to detect hepatic PARP expression in a non-alcoholic steatohepatitis (NASH) mouse model. In this study, male C57BL/6 mice were subjected to a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for a 12-week period to establish preclinical NASH models. [68Ga]DOTA-PARPi PET imaging of the liver was conducted at the 12-week mark after CDAHFD feeding. Comprehensive histopathological analysis, covering hepatic steatosis, inflammation, fibrosis, along with blood biochemistry, was performed in both NASH models and control groups. Despite the induction of severe inflammation, steatosis and fibrosis in the liver of mice with the CDAHFD-NASH model, PET imaging of NASH with [68Ga]-DOTA-PARPi did not reveal a significantly higher uptake in NASH models compared to the control. This underscores the necessity for further development of new chelator-based PARP1 tracers with high binding affinity to enable the visualization of PARP1 changes in NASH pathology.

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聚(ADP-核糖)聚合酶(PARP)靶向 PET 成像在非肿瘤学中的应用:非酒精性脂肪性肝炎临床前模型的试验研究。
多聚(ADP-核糖)聚合酶(PARP)的活化通常预示着脂质代谢的破坏信号,其生理改变可能与非酒精性脂肪肝的发生有关。本研究旨在评估[68Ga]DOTA-PARPi PET在非酒精性脂肪性肝炎(NASH)小鼠模型中检测肝脏PARP表达的能力。在这项研究中,雄性 C57BL/6 小鼠接受了为期 12 周的胆碱缺乏、L-氨基酸定义的高脂肪饮食(CDAHFD),以建立临床前 NASH 模型。喂食CDAHFD 12周后,对肝脏进行[68Ga]DOTA-PARPi PET成像。对 NASH 模型和对照组进行了全面的组织病理学分析,包括肝脏脂肪变性、炎症、纤维化以及血液生化。尽管CDAHFD-NASH模型诱导了小鼠肝脏的严重炎症、脂肪变性和纤维化,但用[68Ga]-DOTA-PARPi对NASH进行正电子发射计算机断层成像时,NASH模型的摄取量并未明显高于对照组。这凸显了进一步开发基于螯合剂的新型 PARP1 示踪剂的必要性,这种示踪剂具有很高的结合亲和力,可使 PARP1 在 NASH 病理学中的变化可视化。
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来源期刊
American journal of nuclear medicine and molecular imaging
American journal of nuclear medicine and molecular imaging RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-
自引率
4.00%
发文量
4
期刊介绍: The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.
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