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在 SCID 小鼠的小细胞肺癌皮下异种移植模型中 I-131 标记的单克隆抗体 ERIC1 的定位和肿瘤生长抑制。

Localization and Tumor Growth Inhibition of I-131-Labeled Monoclonal Antibody ERIC1 in a Subcutaneous Xenograft Model of Small Cell Lung Cancer in SCID Mice.

机构信息

Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.

Institute and Polyclinic for Occupational Medicine, Environmental Medicine, and Preventive Research Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.

出版信息

Int J Mol Sci. 2024 Oct 2;25(19):10638. doi: 10.3390/ijms251910638.

DOI:10.3390/ijms251910638
PMID:39408967
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11477417/
Abstract

This study evaluates the efficacy of [I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation. [I]I-ERIC1 was synthesized with >95% radiochemical purity and a specific activity of 15 TBq/mmol. Tumor activity peaked at 31.5 ± 6.6% ID/g after four days, demonstrating significant antitumor efficacy, which resulted in sustained remission and extended survival. Hematological toxicity was observed, with the optimal dose identified as 2 MBq per animal administered two days post implantation. [I]I-ERIC1 shows promise as a theranostic agent for personalized cancer treatment by effectively targeting SCLC tumors with manageable side effects. However, further studies are required to optimize dosing strategies and minimize toxicity.

摘要

这项研究评估了 [I]I-ERIC1 在靶向和抑制小鼠 SCLC 肿瘤生长方面的疗效,重点关注肿瘤的积累和消退以及潜在的副作用。将 NCAM 阳性 NCI-H69 SCLC 细胞植入 CB17 SCID 小鼠中,并在四个注射后时间点(24、72、96 和 120 小时)测量器官和组织中的 [I]I-ERIC1 生物动力学。实验系列比较了三个治疗组(1、2 或 3 MBq)和对照组之间的肿瘤生长、存活和血液计数变化,治疗分别在植入后两天或五天开始。[I]I-ERIC1 的合成放射性化学纯度 >95%,比活度为 15 TBq/mmol。肿瘤活性在四天后达到 31.5±6.6%ID/g 的峰值,表现出显著的抗肿瘤疗效,导致持续缓解和延长存活。观察到血液学毒性,最佳剂量确定为每只动物 2 MBq,在植入后两天给药。[I]I-ERIC1 有望成为一种治疗癌症的诊断和治疗药物,通过有效靶向 SCLC 肿瘤,同时具有可管理的副作用。然而,需要进一步研究来优化剂量策略并最小化毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c60/11477417/c56218556b64/ijms-25-10638-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c60/11477417/360eb3be4d2c/ijms-25-10638-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c60/11477417/4dd7b81e4f42/ijms-25-10638-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c60/11477417/35beed311b6e/ijms-25-10638-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c60/11477417/c56218556b64/ijms-25-10638-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c60/11477417/360eb3be4d2c/ijms-25-10638-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c60/11477417/4dd7b81e4f42/ijms-25-10638-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c60/11477417/35beed311b6e/ijms-25-10638-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c60/11477417/c56218556b64/ijms-25-10638-g004.jpg

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