Synthesis and biological evaluation of 68Ga-DOTA-AngII as a radiotracer for PET/MR imaging of hepatocellular carcinoma

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-04-30 DOI:10.1016/j.bmc.2025.118221

Ke-Xin Sun , Zhen-Peng Yu , Jia-Lun Luo , Zhi-Qiang Yu , Hong Zhu , Tao Wu , Peng-Fei Dai , Hongwei Si

{"title":"Synthesis and biological evaluation of 68Ga-DOTA-AngII as a radiotracer for PET/MR imaging of hepatocellular carcinoma","authors":"Ke-Xin Sun , Zhen-Peng Yu , Jia-Lun Luo , Zhi-Qiang Yu , Hong Zhu , Tao Wu , Peng-Fei Dai , Hongwei Si","doi":"10.1016/j.bmc.2025.118221","DOIUrl":null,"url":null,"abstract":"<div><div>The precise diagnosis of HCC is confronted with severe challenges due to the tumor heterogeneity and insidious symptoms of hepatocellular carcinoma (HCC), and meanwhile the limitations of positron emission tomography (PET) with traditional 2-deoxy-2-[fluorine-18] fluoro-<span>d</span>-glucose (<sup>18</sup>F-FDG) tracer. Given that angiotensin II type 1 receptor (AT1R) is significantly upregulated in HCC and closely related to its progression, we have developed a novel <sup>68</sup>Ga-radiolabeled compound, <sup>68</sup>Ga-DOTA-AngII (<sup>68</sup>Ga-DOTA-GGDRVYIHPF), and evaluated its HCC detection capability. <sup>68</sup>Ga-DOTA-AngII demonstrated acceptable stability in both human plasma and phosphate buffered saline. In vivo imaging and in vitro biodistribution analysis in tumor-bearing mice showed that <sup>68</sup>Ga-DOTA-AngII demonstrate a high tumor uptake, and the tumor tissue exhibited rapid uptake. In brief, this radiotracer possesses a promising potency for imaging the expression of AT1R for further clinical application.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"125 ","pages":"Article 118221"},"PeriodicalIF":3.3000,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0968089625001622","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The precise diagnosis of HCC is confronted with severe challenges due to the tumor heterogeneity and insidious symptoms of hepatocellular carcinoma (HCC), and meanwhile the limitations of positron emission tomography (PET) with traditional 2-deoxy-2-[fluorine-18] fluoro-d-glucose (¹⁸F-FDG) tracer. Given that angiotensin II type 1 receptor (AT1R) is significantly upregulated in HCC and closely related to its progression, we have developed a novel ⁶⁸Ga-radiolabeled compound, ⁶⁸Ga-DOTA-AngII (⁶⁸Ga-DOTA-GGDRVYIHPF), and evaluated its HCC detection capability. ⁶⁸Ga-DOTA-AngII demonstrated acceptable stability in both human plasma and phosphate buffered saline. In vivo imaging and in vitro biodistribution analysis in tumor-bearing mice showed that ⁶⁸Ga-DOTA-AngII demonstrate a high tumor uptake, and the tumor tissue exhibited rapid uptake. In brief, this radiotracer possesses a promising potency for imaging the expression of AT1R for further clinical application.

Abstract Image

查看原文本刊更多论文

68Ga-DOTA-AngII作为肝细胞癌PET/MR显像示踪剂的合成及生物学评价

由于肝细胞癌（HCC）的肿瘤异质性和隐蔽性，以及传统的2-脱氧-2-[氟-18]氟-葡萄糖（18F-FDG）示踪剂的正电子发射断层扫描（PET）的局限性，HCC的准确诊断面临着严峻的挑战。鉴于血管紧张素II型1受体（angiotensin II type 1 receptor, AT1R）在HCC中显著上调，且与HCC的进展密切相关，我们开发了一种新型68ga放射性标记化合物68Ga-DOTA-AngII (68Ga-DOTA-GGDRVYIHPF)，并对其HCC检测能力进行了评估。68Ga-DOTA-AngII在人血浆和磷酸盐缓冲盐水中均表现出可接受的稳定性。在荷瘤小鼠体内成像和体外生物分布分析表明，68Ga-DOTA-AngII具有较高的肿瘤摄取性，且肿瘤组织摄取迅速。总之，这种放射性示踪剂具有成像AT1R表达的潜力，可用于进一步的临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.