整合素αvβ3放射性示踪剂[18F]F-FPP-RGD2用于监测整合素αv siRNA在NASH肝脏中的药理学作用的评估。

IF 1.3 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Nuclear Medicine and Molecular Imaging Pub Date : 2023-08-01 Epub Date: 2023-03-07 DOI:10.1007/s13139-023-00791-9

Shuichi Hiroyama, Keiko Matsunaga, Miwa Ito, Hitoshi Iimori, Ippei Morita, Jun Nakamura, Eku Shimosegawa, Kohji Abe

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引用次数: 0

摘要

目的：整合素αv是肝纤维化病理生理学中的关键调节因子。在本研究中，我们评估了整合素αvβ3正电子发射断层扫描（PET）放射性示踪剂18F标记的环精氨酸甘氨酸天冬氨酸五肽（[18F]F-FPP-RGD2）在使用整合素αv siRNA检测非酒精性脂肪性肝炎（NASH）模型大鼠肝整合素αv和功能方面的潜在效用，低蛋氨酸、高脂肪饮食8周。在单次静脉注射整合素αv siRNA后1周，对整合素αv蛋白、血清天冬氨酸氨基转移酶和丙氨酸氨基转移酶进行PET/计算机断层扫描成像和定量。整合素αv siRNA使[18F]F-FPP-RGD2的肝脏平均标准摄取值呈剂量依赖性降低。对照组和NASH模型大鼠的平均标准摄取值与整合素αv蛋白水平呈正相关。siRNA注射也降低了NASH模型大鼠的血清天冬氨酸氨基转移酶和丙氨酸氨基转移酶浓度，并与肝脏整合素αv蛋白表达水平相关。结论：本研究表明[18F]F-FPP-RGD2 PET显像是一种很有前途的放射性示踪剂，可用于监测NASH病理中肝脏整合素αv蛋白水平和肝功能。

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Evaluation of an Integrin α_vβ₃ Radiotracer, [¹⁸F]F-FPP-RGD₂, for Monitoring Pharmacological Effects of Integrin α_v siRNA in the NASH Liver.

Purpose: Integrin α_v is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin α_vβ₃ positron emission tomography (PET) radiotracer, ¹⁸F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([¹⁸F]F-FPP-RGD₂), for detecting hepatic integrin α_v and function in nonalcoholic steatohepatitis (NASH) model rats using integrin α_v siRNA.

Methods: NASH model rats were produced by feeding a choline-deficient, low-methionine, high-fat diet for 8 weeks. PET/computerized tomography imaging and quantification of integrin α_v protein, serum aspartate aminotransferase, and alanine aminotransferase were performed 1 week after single intravenous injection of integrin α_v siRNA.

Results: Integrin α_v siRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin α_v protein concentrations in control and NASH model rats. The hepatic mean standard uptake value of [¹⁸F]F-FPP-RGD₂ was decreased dose-dependently by integrin α_v siRNA. The mean standard uptake value was positively correlated with integrin α_v protein levels in control and NASH model rats. Serum aspartate aminotransferase and alanine aminotransferase concentrations were also decreased by siRNA injection and correlated with liver integrin α_v protein expression levels in NASH model rats.

Conclusion: This study suggests that [¹⁸F]F-FPP-RGD₂ PET imaging is a promising radiotracer for monitoring hepatic integrin α_v protein levels and hepatic function in NASH pathology.

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来源期刊

Nuclear Medicine and Molecular Imaging RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-

CiteScore

2.20

自引率

7.70%

发文量

期刊介绍： Nuclear Medicine and Molecular Imaging (Nucl Med Mol Imaging) is an official journal of the Korean Society of Nuclear Medicine, which bimonthly publishes papers on February, April, June, August, October, and December about nuclear medicine and related sciences such as radiochemistry, radiopharmacy, dosimetry and pharmacokinetics / pharmacodynamics of radiopharmaceuticals, nuclear and molecular imaging analysis, nuclear and molecular imaging instrumentation, radiation biology and radionuclide therapy. The journal specially welcomes works of artificial intelligence applied to nuclear medicine. The journal will also welcome original works relating to molecular imaging research such as the development of molecular imaging probes, reporter imaging assays, imaging cell trafficking, imaging endo(exo)genous gene expression, and imaging signal transduction. Nucl Med Mol Imaging publishes the following types of papers: original articles, reviews, case reports, editorials, interesting images, and letters to the editor. The Korean Society of Nuclear Medicine (KSNM) KSNM is a scientific and professional organization founded in 1961 and a member of the Korean Academy of Medical Sciences of the Korean Medical Association which was established by The Medical Services Law. The aims of KSNM are the promotion of nuclear medicine and cooperation of each member. The business of KSNM includes holding academic meetings and symposia, the publication of journals and books, planning and research of promoting science and health, and training and qualification of nuclear medicine specialists.