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[68Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study

文献类型：期刊论文

作者Zhou, Ming2; Xiang, Shijun2; Zhao, Yajie2; Tang, Yongxiang2; Yang, Jinhui2; Yin, Xiaoqin2; Tian, Jie3,4; Hu, Shuo1,2,5; Du, Yang3,6
刊名EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
出版日期2023-09-28
页码11
ISSN号1619-7070
关键词PD-1/PD-L1 Immune checkpoints PET/CT imaging Immunotherapy
DOI10.1007/s00259-023-06447-2
通讯作者Tian, Jie(jie.tian@ia.ac.cn) ; Hu, Shuo(hushuo2018@163.com) ; Du, Yang(yang.du@ia.ac.cn)
英文摘要Purpose PD-L1 PET imaging, as a non-invasive procedure, can perform a real-time, dynamic and quantitative analysis of PD-L1 expression at tumor sites. In this study, we developed a novel peptide-based PET tracer, [(68) Ga]Ga-AUNP-12, for preclinical and first-of-its-kind imaging of PD-L1 expression in patients.Methods Radiosynthesis of [(68) Ga]Ga-AUNP-12 was conducted. Assays for cellular uptake and binding were conducted on the PANC02, CT26, and B16F10 cell lines. Preclinical models were used to investigate its biodistribution, imaging capacity, and pharmacokinetics. Furthermore, interferon-gamma (IFN-gamma) was used for development of an animal model with high PD-L1 expression for targeted PET imaging and efficacy evaluation of PD-L1 blocking therapy. In healthy volunteers and cancer patients, the PD-L1 imaging, radiation dosimetry, safety, and biodistribution were further evaluated.Results In vitro and in vivo animal studies showed that [(68) Ga]Ga-AUNP-12 PET imaging displayed a high specificity in evaluating PD-L1 expression. The radiochemical yield of [(68) Ga]Ga-AUNP-12 was 71.7 +/- 8.2%. Additionally, its molar activity and radiochemical purity were satisfactory. The B16F10 tumor was visualized with the tumor uptake of 6.86 +/- 0.71% ID/g and tumor-to-muscle ratio of 6.83 +/- 0.36 at 60 min after [(68) Ga]Ga-AUNP-12 injection. Furthermore, [(68) Ga]Ga-AUNP-12 PET imaging could sensitively detect the PD-L1 dynamic changes in CT26 tumor xenograft models regulated by IFN-gamma treatment, and correspondingly can effectively guide immunotherapy. Regarding radiation dosimetry, [(68) Ga]Ga-AUNP-12 is safe for human use. The first human study found that [(68) Ga]Ga-AUNP-12 can be rapidly cleared from blood and other nonspecific organs through the kidney excretion, leading to form a clear imaging contrast in the clinical framework. The specificity of [(68) Ga]Ga-AUNP-12 was validated and tumor uptake strongly correlated with the high PD-L1 expression in patients with lung adenocarcinoma and oesophageal squamous cell carcinoma (OSCC).Conclusion [(68) Ga]Ga-AUNP-12 was successfully developed as a PD-L1-specific PET imaging tracer in preclinical and first-in-human studies.
WOS关键词ANTIBODIES ; CANCER ; SAFETY
资助项目National Natural Science Foundation of China[82272111] ; National Natural Science Foundation of China[92159303] ; National Natural Science Foundation of China[62027901] ; National Natural Science Foundation of China[82272045] ; National Natural Science Foundation of China[91859207] ; National Natural Science Foundation of China[81771873] ; National Natural Science Foundation of China[82002887] ; Beijing Natural Science Foundation[7212207] ; Science and Technology Innovation Team Talent Project of Hunan Province[2021RC4056] ; Natural Science Foundation of Hunan Province[2023JJ30976]
WOS研究方向Radiology, Nuclear Medicine & Medical Imaging
语种英语
出版者SPRINGER
WOS记录号WOS:001076672500001
资助机构National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Science and Technology Innovation Team Talent Project of Hunan Province ; Natural Science Foundation of Hunan Province
源URL[http://ir.ia.ac.cn/handle/173211/53086]  
专题自动化研究所_中国科学院分子影像重点实验室
通讯作者Tian, Jie; Hu, Shuo; Du, Yang
作者单位1.Natl Clin Res Ctr Geriatr Disorders, Natl Clin Res Ctr Geriatr Disorders Xiangya, Changsha, Peoples R China
2.Cent South Univ, Xiangya Hosp, Dept Nucl Med, Changsha 410008, Peoples R China
3.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing Key Lab Mol Imaging, 95 Zhongguancun East Rd, Beijing 100190, Peoples R China
4.Beihang Univ, Beijing Adv Innovat Ctr Big Data Based Precis Med, Sch Med, 95 Zhongguancun East Rd, Beijing 100190, Peoples R China
5.Cent South Univ, Xiangya Hosp, Key Lab Biol Nanotechnol Natl Hlth Commiss, Nanotechnol Natl Hlth Commiss, 87 Xiangya Rd, Changsha 410008, Peoples R China
6.Univ Chinese Acad Sci, Beijing 100080, Peoples R China
推荐引用方式
GB/T 7714		 Zhou, Ming,Xiang, Shijun,Zhao, Yajie,et al. [68Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study[J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,2023:11.
APA Zhou, Ming.,Xiang, Shijun.,Zhao, Yajie.,Tang, Yongxiang.,Yang, Jinhui.,...&Du, Yang.(2023).[68Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study.EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,11.
MLA Zhou, Ming,et al."[68Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study".EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING (2023):11.

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