The protein galectin-1 (Gal-1) has been identified as a new PET imaging biomarker for immune checkpoint blockade (ICB) therapy, providing physicians with the ability to predict tumor responses before beginning treatment. The information obtained from Gal-1 PET imaging could be used to facilitate patient stratification and optimize immunotherapy, ultimately leading to targeted interventions and improved patient outcomes. This research was published in the May issue of The Journal of Nuclear Medicine.
Immunotherapies, including ICB, have shown promising clinical outcomes in various types of tumors, although only a subset of patients experience positive outcomes with objective response rates ranging from five to 60 percent. Dr. Zhaofei Liu, a Boya Distinguished Professor at Peking University in Beijing, China, emphasized the importance of developing reliable approaches for assessing responses and selecting eligible patients for immunotherapy. Current clinical criteria for monitoring solid tumor responses to immunotherapy are based on CT and MRI scans, which can result in a delay between treatment commencement and response evaluation. Molecular imaging techniques, such as PET, have emerged as valuable tools for predicting immunotherapy effectiveness through the real-time, quantitative, and noninvasive assessment of biomarkers in vivo.
A mouse model was utilized in the study to identify new imaging biomarkers for tumor responses to ICB therapy. Through a proteomic analysis, researchers discovered that tumors with low Gal-1 expression showed positive responses to ICB therapy. Subsequently, Gal-1 was labeled with 124I and a radiotracer (124I-α-Gal-1) was created for small animal PET imaging and biodistribution studies to assess the specificity of the radiotracer. PET imaging with 124I-α-Gal-1 revealed the immunosuppressive status of the tumor microenvironment, enabling the prediction of ICB resistance prior to treatment initiation. For tumors that were not predicted to respond well to ICB therapy, researchers developed a rescue strategy utilizing a Gal-1 inhibitor that significantly increased the chances of success.
Dr. Liu emphasized that Gal-1 PET imaging provides a means for predicting ICB efficacy early on, before treatment initiation, and facilitates the precise design of combinational regimes. This sensitive approach has the potential to achieve individualized precision treatment for patients in the future. The study was published online in March 2024, highlighting the potential impact of Gal-1 PET imaging in improving patient outcomes through targeted immunotherapy interventions. The findings of this research represent a significant advancement in the field of immunotherapy and may lead to more personalized and effective treatment approaches for patients with various types of tumors.