Preclinical Evaluation and Pilot Clinical Study of CD137 PET Radiotracer for Noninvasive Monitoring Early Responses of Immunotherapy
文献类型：期刊论文
| 作者 | Cheng, Kai7,8; Ge, Luna5,6; Song, Miaomiao3,4; Li, Wanhu7; Zheng, Jinsong7; Liu, Jingru8; Luo, Yuxi8; Sun, Pengfei2; Xu, Shengnan8; Cheng, Zhen1,3,4 |
| 刊名 | JOURNAL OF NUCLEAR MEDICINE
 |
| 出版日期 | 2025 |
| 卷号 | 66期号:1页码:40-46 |
| 关键词 | PET imaging CD137 activated T cells immunotherapy |
| ISSN号 | 0161-5505 |
| DOI | 10.2967/jnumed.124.268068 |
| 英文摘要 | Given the variability in the effectiveness of immune checkpoint blocking therapy among patients and tumor types, development of noninvasive methods for longitudinal assessment of immune cell function and early tumor response is crucial for precision immunotherapy. CD137 (4-1BB), a marker of activated T cells, plays a significant role in immunotherapy. However, its potential as an imaging biomarker for activated T cells in the tumor microenvironment has not been explored. This study introduces a bicyclic peptide-based probe that targets CD137 for noninvasive PET imaging of tumor-infiltrating activated T cells. Methods: A bicyclic peptide-based probe, [18F]AlF- NOTA-BCP137, was first designed and synthesized for quantitative and longitudinal whole-body visualization of CD137 dynamics. Initially, [18F]AlF-NOTA-BCP137 was assessed in mouse models with varying CD137 expression levels. Next, [18F]AlF-NOTA-BCP137 was used for longitudinal monitoring of systemic CD137 changes in a humanized tumor-bearing mouse model. Lastly, the probe was further evaluated in a small group of patients with hepatocellular carcinoma undergoing immunotherapy or combination immunotherapy. Results: [18F]AlF- NOTA-BCP137 PET accurately characterized CD137 expression in homologous transplanted mouse models and tumor patients. The findings from animal studies indicated that uptake of [18F]AlF-NOTA- BCP137 was predictive of the early therapeutic response to combination immunotherapies and was positively associated with the increased survival rates of mice with tumors. A preliminary clinical study involving small patient cohorts demonstrated that [18F]AlF-NOTA-BCP137 imaging effectively predicted early patient responses to immunotherapeutic interventions. Conclusion: [18F]AlF-NOTA-BCP137 PET imaging of CD137 is a promising and reliable method for evaluating the efficacy of multiple combination immunotherapies and merits further validation in larger-scale clinical trials. This approach has the potential for early noninvasive visualization of individual patient responses in combination cancer immunotherapy and will aid in tailoring personalized strategies for patients. |
| WOS关键词 | T-CELLS ; EXPRESSION ; CHALLENGES ; SURVIVAL ; 4-1BB |
| 资助项目 | National Natural Science Founda-tion of China[8,22,03,014] ; Natural Science Foundation of Shandong Province[ZR2020QH327] ; Natural Science Foundation of Shandong Province[ZR2022QB015] ; China Postdoctoral Science Foundation[2023M742149] ; Taishan Scholars Program of Shandong Province[tsqn202306386] |
| WOS研究方向 | Radiology, Nuclear Medicine & Medical Imaging |
| 语种 | 英语 |
| WOS记录号 | WOS:001392592700009 |
| 出版者 | SOC NUCLEAR MEDICINE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315663]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Cheng, Zhen; Yu, Jinming; Liu, Jie |
| 作者单位 | 1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Peoples R China 2.Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept Hepatobiliary Surg, Jinan, Peoples R China 3.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, State Key Lab Drug Res, Shanghai, Peoples R China 5.Shandong First Med Univ & Shandong Acad Med Sci, Shandong Med Biotechnol Ctr, Jinan, Peoples R China 6.Shandong First Med Univ & Shandong Acad Med Sci, Biomed Sci Coll, Jinan, Peoples R China 7.Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept PET CT Ctr, Jinan, Peoples R China 8.Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Shandong Prov Key Lab Precis Oncol, Jinan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cheng, Kai,Ge, Luna,Song, Miaomiao,et al. Preclinical Evaluation and Pilot Clinical Study of CD137 PET Radiotracer for Noninvasive Monitoring Early Responses of Immunotherapy[J]. JOURNAL OF NUCLEAR MEDICINE,2025,66(1):40-46. |
| APA | Cheng, Kai.,Ge, Luna.,Song, Miaomiao.,Li, Wanhu.,Zheng, Jinsong.,...&Liu, Jie.(2025).Preclinical Evaluation and Pilot Clinical Study of CD137 PET Radiotracer for Noninvasive Monitoring Early Responses of Immunotherapy.JOURNAL OF NUCLEAR MEDICINE,66(1),40-46. |
| MLA | Cheng, Kai,et al."Preclinical Evaluation and Pilot Clinical Study of CD137 PET Radiotracer for Noninvasive Monitoring Early Responses of Immunotherapy".JOURNAL OF NUCLEAR MEDICINE 66.1(2025):40-46. |
入库方式： OAI收割
来源：上海药物研究所
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