前列腺特异性膜抗原有望成为使用[177Lu]Lu-PSMA-I&T 对三阴性乳腺癌进行内源性放射治疗的血管靶点

IF 6.1 1区 医学 Q1 ONCOLOGY Breast Cancer Research Pub Date : 2024-02-20 DOI:10.1186/s13058-024-01787-9
Amelie Heesch, Alexandru Florea, Jochen Maurer, Pardes Habib, Laura S. Werth, Thomas Hansen, Elmar Stickeler, Sabri E. M. Sahnoun, Felix M. Mottaghy, Agnieszka Morgenroth
{"title":"前列腺特异性膜抗原有望成为使用[177Lu]Lu-PSMA-I&T 对三阴性乳腺癌进行内源性放射治疗的血管靶点","authors":"Amelie Heesch, Alexandru Florea, Jochen Maurer, Pardes Habib, Laura S. Werth, Thomas Hansen, Elmar Stickeler, Sabri E. M. Sahnoun, Felix M. Mottaghy, Agnieszka Morgenroth","doi":"10.1186/s13058-024-01787-9","DOIUrl":null,"url":null,"abstract":"Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC. Rj:NMRI-Foxn1nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography. Tumor volumes were significantly smaller in the single dose (p < 0.001) and fractionated dose (p < 0.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [177Lu]Lu-PSMA-I&T decreased the size of viable tumor areas. We further demonstrated, that [177Lu]Lu-PSMA-I&T binds specifically to the tumor-associated vasculature. This study highlights the potential of [177Lu]Lu-PSMA-I&T for endogenous radiotherapy of TNBC. ","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"161 1","pages":""},"PeriodicalIF":6.1000,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The prostate-specific membrane antigen holds potential as a vascular target for endogenous radiotherapy with [177Lu]Lu-PSMA-I&T for triple-negative breast cancer\",\"authors\":\"Amelie Heesch, Alexandru Florea, Jochen Maurer, Pardes Habib, Laura S. Werth, Thomas Hansen, Elmar Stickeler, Sabri E. M. Sahnoun, Felix M. Mottaghy, Agnieszka Morgenroth\",\"doi\":\"10.1186/s13058-024-01787-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC. Rj:NMRI-Foxn1nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography. Tumor volumes were significantly smaller in the single dose (p < 0.001) and fractionated dose (p < 0.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [177Lu]Lu-PSMA-I&T decreased the size of viable tumor areas. We further demonstrated, that [177Lu]Lu-PSMA-I&T binds specifically to the tumor-associated vasculature. This study highlights the potential of [177Lu]Lu-PSMA-I&T for endogenous radiotherapy of TNBC. \",\"PeriodicalId\":9222,\"journal\":{\"name\":\"Breast Cancer Research\",\"volume\":\"161 1\",\"pages\":\"\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-02-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Breast Cancer Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13058-024-01787-9\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13058-024-01787-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

前列腺特异性膜抗原(PSMA)在三阴性乳腺癌(TNBC)血管上的过度表达为使用[177Lu]Lu-PSMA-I&T进行靶向内放射治疗提供了一个前景广阔的途径。本研究旨在评估和比较单剂量与分剂量[177Lu]Lu-PSMA-I&T在TNBC正位模型中的疗效。Rj:NMRI-Foxn1nu/nu小鼠是MDA-MB-231异种移植物的受体。单剂量组接受1 × 60 ± 5 MBq剂量的[177Lu]Lu-PSMA-I&T治疗,分剂量组接受4 × 15 ± 2 MBq剂量的[177Lu]Lu-PSMA-I&T治疗,间隔7天。对照组接受 0.9% NaCl。使用[18F]FDG-PET/CT监测肿瘤进展。体内外分析包括免疫染色、TUNEL染色、H&E染色、显微自动放射摄影和自动放射摄影。单剂量组(p < 0.001)和分剂量组(p < 0.001)的肿瘤体积明显较小。肿瘤生长抑制率分别为 38%(单剂量)和 30%(分次剂量)。与对照组相比,治疗组的中位生存期明显延长(单剂量组、分剂量组和对照组的中位生存期分别为31天、28天和19天)。[177Lu]Lu-PSMA-I&T能缩小存活肿瘤区域的大小。我们进一步证实,[177Lu]Lu-PSMA-I&T 能与肿瘤相关血管特异性结合。这项研究凸显了[177Lu]Lu-PSMA-I&T在TNBC内源性放射治疗中的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
The prostate-specific membrane antigen holds potential as a vascular target for endogenous radiotherapy with [177Lu]Lu-PSMA-I&T for triple-negative breast cancer
Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC. Rj:NMRI-Foxn1nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography. Tumor volumes were significantly smaller in the single dose (p < 0.001) and fractionated dose (p < 0.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [177Lu]Lu-PSMA-I&T decreased the size of viable tumor areas. We further demonstrated, that [177Lu]Lu-PSMA-I&T binds specifically to the tumor-associated vasculature. This study highlights the potential of [177Lu]Lu-PSMA-I&T for endogenous radiotherapy of TNBC.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Breast Cancer Research
Breast Cancer Research 医学-肿瘤学
自引率
0.00%
发文量
76
期刊介绍: Breast Cancer Research is an international, peer-reviewed online journal, publishing original research, reviews, editorials and reports. Open access research articles of exceptional interest are published in all areas of biology and medicine relevant to breast cancer, including normal mammary gland biology, with special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal publishes preclinical, translational and clinical studies with a biological basis, including Phase I and Phase II trials.
期刊最新文献
Impact of an online decision support tool for ductal carcinoma in situ (DCIS) using a pre-post design (AFT-25) Safety and efficacy of topical testosterone in breast cancer patients receiving ovarian suppression and aromatase inhibitor therapy A triple hormone receptor ER, AR, and VDR signature is a robust prognosis predictor in breast cancer Characteristics and transcriptional regulators of spontaneous epithelial–mesenchymal transition in genetically unperturbed patient-derived non-spindled breast carcinoma CAR expression in invasive breast carcinoma and its effect on adenovirus transduction efficiency
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1