用于 TNBC PD-L1 体内表达非侵入性评估的放射性标记 Atezolizumab 的初步研究。

IF 0.9 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-08-30 DOI:10.1002/jlcr.4122
Shuhua He, Lina Jia, Xiaobei Zheng, Yang Wang, Yuxia Liu, Lan Zhang
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引用次数: 0

摘要

程序性死亡配体1(PD-L1)的表达与三阴性乳腺癌的疗效和预后有关。本研究采用间接标记法合成了[125I]PI-Atezolizumab。通过在磷酸盐缓冲盐水和胎牛血清中培养,评估了[125I]PI-Atezolizumab的体外稳定性。通过体外孵育评估了[125I]PI-Atezolizumab与表达人源化PD-L1的MDA-MB-231细胞的特异性结合,其Kd值与Atezolizumab相当。这表明标记过程并没有影响 Atezolizumab 与 PD-L1 的亲和力。随后,研究人员在正常小鼠体内进行了药代动力学研究,并在肿瘤小鼠体内进行了生物分布实验。对[125I]PI-Atezolizumab和125I标记的Atezolizumab的生物分布结果进行比较后发现,前者的体内稳定性更好。单光子发射计算机断层扫描(SPECT)/CT成像进一步证实了[125I]PI-Atezolizumab对MDA-MB-231异种移植物中PD-L1的靶向特异性,免疫组化染色也验证了这一点。这项研究强调了通过间接标记法制备的[125I]PI-Atezolizumab在三阴性乳腺癌模型中监测PD-L1的实用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Preliminary Research of Radiolabeled Atezolizumab for the Noninvasive Evaluation of TNBC PD-L1 Expression In Vivo

Programmed death-ligand 1 (PD-L1) expression is related to the efficacy and prognosis in triple-negative breast cancer. This study employed an indirect labeling method to synthesize [125I]PI-Atezolizumab. The in vitro stability of [125I]PI-Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [125I]PI-Atezolizumab to MDA-MB-231 cells expressing humanized PD-L1 was assessed through in vitro incubation, yielding a Kd value comparable to that of Atezolizumab. This suggests that the labeling process did not compromise the affinity of the Atezolizumab to PD-L1. Subsequently, pharmacokinetic studies were conducted in normal mice and biodistribution experiments in tumor-bearing mice. A comparison of the biodistribution results between [125I]PI-Atezolizumab and 125I-labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [125I]PI-Atezolizumab for PD-L1 in MDA-MB-231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [125I]PI-Atezolizumab, prepared via indirect labeling, for monitoring PD-L1 in triple-negative breast cancer models.

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来源期刊
CiteScore
3.30
自引率
0.00%
发文量
57
审稿时长
1 months
期刊介绍: The Journal of Labelled Compounds and Radiopharmaceuticals publishes all aspects of research dealing with labeled compound preparation and applications of these compounds. This includes tracer methods used in medical, pharmacological, biological, biochemical and chemical research in vitro and in vivo. The Journal of Labelled Compounds and Radiopharmaceuticals devotes particular attention to biomedical research, diagnostic and therapeutic applications of radiopharmaceuticals, covering all stages of development from basic metabolic research and technological development to preclinical and clinical studies based on physically and chemically well characterized molecular structures, coordination compounds and nano-particles.
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