Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts.

IF 1.7 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Open Medicine Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI:10.1515/med-2024-1027
Xianwen Hu, Hongyu Hu, Dandan Li, Pan Wang, Jiong Cai
{"title":"Affibody-based molecular probe <sup>99m</sup>Tc-(HE)<sub>3</sub>Z<sub>HER2:V2</sub> for non-invasive HER2 detection in ovarian and breast cancer xenografts.","authors":"Xianwen Hu, Hongyu Hu, Dandan Li, Pan Wang, Jiong Cai","doi":"10.1515/med-2024-1027","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess the biodistribution and bioactivity of the affibody molecular probe <sup>99m</sup>Tc-(HE)<sub>3</sub>Z<sub>HER2:V2</sub>, prepared by genetic recombination, and to investigate its potential for targeted human epidermal growth factor receptor 2 (HER2) imaging in SKOV3 ovarian cancer and MDA-MB-361 breast cancer xenografts.</p><p><strong>Methods: </strong>Affibody molecules were generated through genetic recombination. The radiochemical purity of the <sup>99m</sup>Tc-labeled HER2 affibody was determined using reverse phase high performance liquid chromatography (RP-HPLC). Evaluation of HER2 affinity in SKOV3 ovarian cancer cells and MDA-MB-361 breast cancer cells (HER2-positive) was conducted by calculating equilibrium dissociation constants. Biodistribution of the <sup>99m</sup>Tc-labeled affibody molecular probe was assessed in Balb/c mice bearing SKOV3 tumors. Tumor targeting specificity was evaluated in Balb/c mice using SKOV3, MDA-MB-361, and AT-3 (HER2-negative) xenografts.</p><p><strong>Results: </strong>Affibody (HE)<sub>3</sub>Z<sub>HER2:V2</sub>, generated through recombinant gene expression, was successfully labeled with <sup>99m</sup>Tc, achieving a radiochemical purity of (96.0 ± 1.7)% (<i>n</i> = 3) as determined by RP-HPLC. This molecular probe exhibited specific binding to HER2-positive SKOV3 cells, demonstrating intense radioactive uptake. Biodistribution analysis showed rapid accumulation of <sup>99m</sup>Tc-(HE)<sub>3</sub>Z<sub>HER2:V2</sub> in HER2-positive tumors post-administration, primarily clearing through the urinary system. Single-photon emission computed tomography imaging conducted 1-3 h after intravenous injection of <sup>99m</sup>Tc-(HE)<sub>3</sub>Z<sub>HER2:V2</sub> into HER2-positive SKOV3 and MDA-MB-361 nude mouse models confirmed targeted uptake of the molecular probe by the tumors.</p><p><strong>Conclusions: </strong>The molecular probe <sup>99m</sup>Tc-(HE)<sub>3</sub>Z<sub>HER2:V2</sub> developed in this study effectively targets HER2 for imaging HER2-positive SKOV3 and MDA-MB-361 xenografts <i>in vivo</i>. It exhibits rapid blood clearance without evident toxic effects, suggesting its potential as a valuable marker for detecting HER2 expression in tumor cells.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"19 1","pages":"20241027"},"PeriodicalIF":1.7000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377979/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Open Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1515/med-2024-1027","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose: This study aimed to assess the biodistribution and bioactivity of the affibody molecular probe 99mTc-(HE)3ZHER2:V2, prepared by genetic recombination, and to investigate its potential for targeted human epidermal growth factor receptor 2 (HER2) imaging in SKOV3 ovarian cancer and MDA-MB-361 breast cancer xenografts.

Methods: Affibody molecules were generated through genetic recombination. The radiochemical purity of the 99mTc-labeled HER2 affibody was determined using reverse phase high performance liquid chromatography (RP-HPLC). Evaluation of HER2 affinity in SKOV3 ovarian cancer cells and MDA-MB-361 breast cancer cells (HER2-positive) was conducted by calculating equilibrium dissociation constants. Biodistribution of the 99mTc-labeled affibody molecular probe was assessed in Balb/c mice bearing SKOV3 tumors. Tumor targeting specificity was evaluated in Balb/c mice using SKOV3, MDA-MB-361, and AT-3 (HER2-negative) xenografts.

Results: Affibody (HE)3ZHER2:V2, generated through recombinant gene expression, was successfully labeled with 99mTc, achieving a radiochemical purity of (96.0 ± 1.7)% (n = 3) as determined by RP-HPLC. This molecular probe exhibited specific binding to HER2-positive SKOV3 cells, demonstrating intense radioactive uptake. Biodistribution analysis showed rapid accumulation of 99mTc-(HE)3ZHER2:V2 in HER2-positive tumors post-administration, primarily clearing through the urinary system. Single-photon emission computed tomography imaging conducted 1-3 h after intravenous injection of 99mTc-(HE)3ZHER2:V2 into HER2-positive SKOV3 and MDA-MB-361 nude mouse models confirmed targeted uptake of the molecular probe by the tumors.

Conclusions: The molecular probe 99mTc-(HE)3ZHER2:V2 developed in this study effectively targets HER2 for imaging HER2-positive SKOV3 and MDA-MB-361 xenografts in vivo. It exhibits rapid blood clearance without evident toxic effects, suggesting its potential as a valuable marker for detecting HER2 expression in tumor cells.

基于亲和素的分子探针 99mTc-(HE)3ZHER2:V2 用于卵巢癌和乳腺癌异种移植物中 HER2 的无创检测。
目的:本研究旨在评估通过基因重组制备的亲和抗体分子探针 99mTc-(HE)3ZHER2:V2 的生物分布和生物活性,并探讨其在 SKOV3 卵巢癌和 MDA-MB-361 乳腺癌异种移植中进行人表皮生长因子受体 2 (HER2) 靶向成像的潜力:方法:通过基因重组生成亲和体分子。采用反相高效液相色谱法(RP-HPLC)测定了 99mTc 标记的 HER2 亲和体的放射化学纯度。通过计算平衡解离常数,评估了 HER2 在 SKOV3 卵巢癌细胞和 MDA-MB-361 乳腺癌细胞(HER2 阳性)中的亲和力。在携带 SKOV3 肿瘤的 Balb/c 小鼠体内评估了 99mTc 标记的亲和抗体分子探针的生物分布。使用SKOV3、MDA-MB-361和AT-3(HER2阴性)异种移植物在Balb/c小鼠中评估了肿瘤靶向特异性:通过重组基因表达生成的Affibody (HE)3ZHER2:V2成功标记了99m锝,经RP-HPLC测定,放射化学纯度为(96.0 ± 1.7)%(n = 3)。该分子探针与 HER2 阳性的 SKOV3 细胞特异性结合,表现出强烈的放射性吸收。生物分布分析表明,给药后,99m锝-(HE)3ZHER2:V2 在 HER2 阳性肿瘤中迅速积累,主要通过泌尿系统清除。在HER2阳性的SKOV3和MDA-MB-361裸鼠模型中静脉注射99m锝-(HE)3ZHER2:V2 1-3小时后进行的单光子发射计算机断层扫描成像证实了肿瘤对分子探针的靶向摄取:本研究开发的分子探针99m锝-(HE)3ZHER2:V2能有效靶向HER2,用于体内HER2阳性SKOV3和MDA-MB-361异种移植物的成像。它在血液中清除迅速,无明显毒性反应,这表明它有潜力成为检测肿瘤细胞中 HER2 表达的重要标记物。
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
Open Medicine
Open Medicine Medicine-General Medicine
CiteScore
3.00
自引率
0.00%
发文量
153
审稿时长
20 weeks
期刊介绍: Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信