Immunotherapies, such as immune checkpoint blockade (ICB), have shown promising clinical results in treating melanoma, non-small cell lung cancer, and other tumor types. However, the effectiveness of these therapies varies significantly, with objective response rates ranging from five to 60% among patients. There is a pressing need for reliable methods to assess responses and determine which patients are likely to benefit from immunotherapy. Traditional approaches for monitoring solid tumor responses, which rely on CT and MRI scans, often lead to significant delays in measuring the effects of treatment. In contrast, molecular imaging techniques, particularly PET, offer a dynamic and non-invasive way to evaluate biomarkers in vivo, providing a promising method for predicting the effectiveness of immunotherapy in real time.

Now, researchers at Peking University (Beijing, China) have identified the protein galectin-1 (Gal-1) as a new PET imaging biomarker for ICB therapy, enabling doctors to predict tumor responses before treatment begins. Utilizing Gal-1 PET imaging can also help in patient stratification and the optimization of immunotherapy treatments, potentially enhancing patient outcomes. In their study, the team used a mouse model to search for novel imaging biomarkers that could indicate how tumors respond to ICB therapy. Proteomic analysis revealed that tumors with low Gal-1 expression were more likely to respond favorably to ICB therapy.

The researchers then proceeded to label Gal-1 with 124I to create a radiotracer (124I-α-Gal-1) and conducted small animal PET imaging and biodistribution studies to verify the tracer’s specificity. PET imaging with 124I-αGal-1 effectively indicated the immunosuppressive status of the tumor microenvironment, allowing for the early prediction of ICB resistance. For tumors predicted not to respond well to ICB, the researchers devised a rescue strategy using a Gal-1 inhibitor, which significantly enhanced the likelihood of successful treatment.

“Gal-1 PET opens avenues for the early prediction of ICB efficacy before treatment initiation and facilitates the precision design of combinational regimes,” said Zhaofei Liu, PhD, Boya Distinguished Professor at Peking University. “This sensitive approach has the potential to achieve individualized precision treatment for patients in the future.” 

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