Shuhua He, Lina Jia, Xiaobei Zheng, Yang Wang, Yuxia Liu, Lan Zhang
{"title":"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。","authors":"Shuhua He, Lina Jia, Xiaobei Zheng, Yang Wang, Yuxia Liu, Lan Zhang","doi":"10.1002/jlcr.4122","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>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 [<sup>125</sup>I]PI-Atezolizumab. The in vitro stability of [<sup>125</sup>I]PI-Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [<sup>125</sup>I]PI-Atezolizumab to MDA-MB-231 cells expressing humanized PD-L1 was assessed through in vitro incubation, yielding a <i>K</i><sub>d</sub> 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 [<sup>125</sup>I]PI-Atezolizumab and <sup>125</sup>I-labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [<sup>125</sup>I]PI-Atezolizumab for PD-L1 in MDA-MB-231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [<sup>125</sup>I]PI-Atezolizumab, prepared via indirect labeling, for monitoring PD-L1 in triple-negative breast cancer models.</p>\n </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 11","pages":"384-391"},"PeriodicalIF":0.9000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Preliminary Research of Radiolabeled Atezolizumab for the Noninvasive Evaluation of TNBC PD-L1 Expression In Vivo\",\"authors\":\"Shuhua He, Lina Jia, Xiaobei Zheng, Yang Wang, Yuxia Liu, Lan Zhang\",\"doi\":\"10.1002/jlcr.4122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>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 [<sup>125</sup>I]PI-Atezolizumab. The in vitro stability of [<sup>125</sup>I]PI-Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [<sup>125</sup>I]PI-Atezolizumab to MDA-MB-231 cells expressing humanized PD-L1 was assessed through in vitro incubation, yielding a <i>K</i><sub>d</sub> 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 [<sup>125</sup>I]PI-Atezolizumab and <sup>125</sup>I-labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [<sup>125</sup>I]PI-Atezolizumab for PD-L1 in MDA-MB-231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [<sup>125</sup>I]PI-Atezolizumab, prepared via indirect labeling, for monitoring PD-L1 in triple-negative breast cancer models.</p>\\n </div>\",\"PeriodicalId\":16288,\"journal\":{\"name\":\"Journal of labelled compounds & radiopharmaceuticals\",\"volume\":\"67 11\",\"pages\":\"384-391\"},\"PeriodicalIF\":0.9000,\"publicationDate\":\"2024-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of labelled compounds & radiopharmaceuticals\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jlcr.4122\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of labelled compounds & radiopharmaceuticals","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jlcr.4122","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
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.
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.