Preclinical Evaluation and Pilot Clinical Study of CD137 PET Radiotracer for Noninvasive Monitoring Early Responses of Immunotherapy

作者：Kai Cheng, Luna Ge, Miaomiao Song, Wanhu Li, Jinsong Zheng, Jingru Liu, Yuxi Luo, Pengfei Sun, Shengnan Xu, Zhen Cheng, Jinming Yu, Jie Liu · 发表于：Journal of Nuclear Medicine · 年份：2024 · DOI：10.2967/jnumed.124.268068 · 被引用次数：8 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Cancer Cells and Metastasis

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, [ 18 F]AlF-NOTA-BCP137, was first designed and synthesized for quantitative and longitudinal whole-body visualization of CD137 dynamics. Initially, [ 18 F]AlF-NOTA-BCP137 was assessed in mouse models with varying CD137 expression levels. Next, [ 18 F]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: [ 18 F]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 [ 18 F]AlF-NOTA-BCP137 was predictive of the early therapeutic response to combination immunotherapies and was posit...