Newly Identified PET Biomarker Predicts Success of Immune Checkpoint Blockade Therapy

May 7, 2024

Reston, VA—The protein galectin-1 (Gal-1) has been identified as a new PET imaging biomarker for immune checkpoint blockade (ICB) therapy, allowing physicians to predict the tumor responses before beginning treatment. Information garnered from Gal-1 PET imaging could also be used to facilitate patient stratification and optimize immunotherapy, enabling targeted interventions and improving patient outcomes. This research was published in the May issue of The Journal of Nuclear Medicine.

Immunotherapies, such as ICB, have produced promising clinical outcomes in melanoma, non–small cell lung cancer, and several other types of tumors. However, only a subgroup of patients experiences positive outcomes with objective response rates spanning between five and 60 percent. 

“Developing reliable approaches for assessing responses and selecting eligible patients for immunotherapy remains challenging,” said Zhaofei Liu, PhD, Boya Distinguished Professor at Peking University in Beijing, China. “Current clinical criteria for monitoring solid tumor responses to immunotherapy are based on CT and MRI scans, but these methods result in a considerable delay between treatment commencement and response evaluation. Molecular imaging techniques, especially PET, have emerged as robust tools for predicting immunotherapy effectiveness through the real-time, quantitative, and noninvasive assessment of biomarkers in vivo.”

In the study, a mouse model was utilized to identify new imaging biomarkers for tumor responses to ICB therapy. Through a proteomic analysis (separation, identification, and quantification of proteins in a tumor), researchers found that tumors exhibiting low Gal-1 expression responded positively to ICB therapy.

Next, Gal-1 was labeled with 124I and the radiotracer (124I-α-Gal-1) and small animal PET imaging and biodistribution studies were conducted to assess the specificity of the radiotracer. PET imaging with 124I-αGal-1 showed the immunosuppressive status of the tumor microenvironment, thus enabling the prediction of ICB resistance in advance of treatment. For tumors that were not predicted to respond well to ICB therapy, researchers developed a rescue strategy that utilized a Gal-1 inhibitor that significantly improved the chance for success.

“Gal-1 PET opens avenues for the early prediction of ICB efficacy before treatment initiation and facilitates the precision design of combinational regimes,” noted Liu. “This sensitive approach has the potential to achieve individualized precision treatment for patients in the future.”

Figure 4. PET imaging of 124I-αGal-1 predicts ICB therapy. (A) PET/CT images and quantified tumor uptake of 124I-αGal-1 72 h after injection in 4T1 tumor–bearing mice, classified into high- and low-tumor-uptake groups (cutoff, 3.4 percentage injected dose per gram [%ID/g]) (n = 4/group). White arrows indicate tumors. (B) Tumor growth curves for 4T1 tumor–bearing mice in high- and low-tumor-uptake groups of 124I-αGal-1 after ICB therapy (n = 5/group). (C) Western blot analysis and quantitative assessment of Gal-1 levels in high- and low-tumor-uptake groups of 124I-αGal-1 (n = 4/group). All numeric data are presented as mean ± SD. *P < 0.05; **P < 0.01. α = anti-; i.p. = intraperitoneally.

 

The authors of “Noninvasively Deciphering the Immunosuppressive Tumor Microenvironment Using Galectin-1 PET to Inform Immunotherapy Responses” include Ning Liu, Xiujie Yang, Chao Gao, Jianze Wang, Yuwen Zeng, Linyu Zhang, Qi Yin, Ting Zhang, Haoyi Zhou, Kui Li, and Jinhong Du, Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Shixin Zhou, Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Xuyang Zhao, Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Hua Zhu and Zhi Yang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China; and Zhaofei Liu, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China, Department of Nuclear Medicine, Peking University Third Hospital, Beijing, China, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China, and Peking University–Yunnan Baiyao International Medical Research Center, Beijing, China.

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