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用生物素化 D-D 构建体和 Tc-DTPA-生物素进行靶向放射免疫成像:小细胞肺癌早期诊断的策略。

Pretargeted radioimmunoimaging with a biotinylated D-D construct and Tc-DTPA-biotin: strategies for early diagnosis of small cell lung cancer.

机构信息

Department of Nuclear Medicine, The Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P. R China.

Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou City, Jiangsu Province, P. R China.

出版信息

J Int Med Res. 2020 Jul;48(7):300060520937162. doi: 10.1177/0300060520937162.

Abstract

OBJECTIVE

Pro-gastrin releasing peptide (ProGRP) plays an oncogenic role in small cell lung cancer (SCLC). The anti-ProGRP monoclonal antibody D-D can selectively accumulate in SCLC xenografts in nude mice. This study evaluated the effectiveness of a new pretargeting procedure for the early diagnosis of SCLC.

METHODS

D-D was radiolabeled with technetium-99m (Tc) using a three-step pretargeting method. Mice with SCLC xenografts were treated with different labeling regimens, and the biodistribution and radioimmunoimaging were explored. The percentage injected dose per gram (%ID/g) in various organs, tumor/non-tumor (T/NT) ratio, and tumor/background (T/B) ratio were also calculated.

RESULTS

distribution experiments revealed that Tc-DTPA-biotin was metabolized in the liver and kidney, with rapid elimination in the blood. The T/B ratio was highest in mice treated with biotinylated antibody D-D + avidin + Tc-DTPA-biotin. Single-photon emission computerized tomography imaging further confirmed that the T/B ratio was highest in this group at all time points.

CONCLUSIONS

In contrast to directly labeled D-D, pretargeting technology displayed specific enhancement and signal amplification in tumors, which could increase the target tumor uptake of Tc and provide a new approach for the early diagnosis of SCLC.

摘要

目的

胃泌素释放肽前体(ProGRP)在小细胞肺癌(SCLC)中发挥致癌作用。抗 ProGRP 单克隆抗体 D-D 可选择性地在裸鼠的 SCLC 异种移植瘤中积聚。本研究评估了一种新的靶向前体方法用于 SCLC 早期诊断的有效性。

方法

采用三步靶向前体法对 D-D 进行锝-99m(Tc)标记。用不同的标记方案处理带有 SCLC 异种移植瘤的小鼠,探索其生物分布和放射免疫成像。还计算了各器官的注射剂量百分比(%ID/g)、肿瘤/非肿瘤(T/NT)比和肿瘤/背景(T/B)比。

结果

分布实验表明,Tc-DTPA-生物素在肝脏和肾脏中被代谢,血液中的清除速度很快。用生物素化抗体 D-D+亲和素+Tc-DTPA-生物素处理的小鼠 T/B 比值最高。单光子发射计算机断层扫描成像进一步证实,在所有时间点,该组的 T/B 比值最高。

结论

与直接标记的 D-D 相比,靶向前体技术在肿瘤中显示出特异性增强和信号放大,可增加 Tc 的靶肿瘤摄取,并为 SCLC 的早期诊断提供一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/698e/7375734/9ab82477a9a2/10.1177_0300060520937162-fig1.jpg

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