New biomarker allows doctors to predict tumor response before treatment

The protein galectin-1 (Gal-1) has been identified as a new biomarker for PET imaging used in checkpoint blockade (ICB) immunotherapy, allowing physicians to predict tumor response before treatment.

Information obtained from Gal-1 PET imaging can also be used to stratify patients and optimize immunotherapy, allowing for targeted interventions and improved patient outcomes. This study was published in the May issue of The Journal of Nuclear Medicine.

Immunotherapies such as ICB have shown encouraging clinical results in melanoma, non-small cell lung cancer and several other types of tumors. However, only a subset of patients experience positive results, with objective response rates ranging from 5% to 60%.

“Developing reliable approaches to assess responses and select suitable patients for immunotherapy remains challenging,” said Zhaofei Liu, PhD, Distinguished Professor at Peking University in China.

"Current clinical criteria for monitoring responses to immunotherapy in solid tumors are based on CT and MRI, but these methods result in a significant delay between initiation of treatment and assessment of response. Molecular imaging techniques, especially PET, have become reliable tools for predicting the effectiveness of immunotherapy through quantitative and non-invasive assessment of biomarkers in real time."

124I-αGal-1 PET scan predicts response to immune checkpoint inhibitor (ICB) therapy. Source: N Liu and X Yang et al., Peking University, Beijing, China.

The study used a mouse model to identify new imaging biomarkers of tumor responses to ICB therapy. Through proteomic analysis (separating, identifying and quantifying proteins in a tumor), the researchers found that tumors with low Gal-1 expression responded positively to ICB therapy.

Gal-1 was then labeled with 124I, and a radiotracer (124I-α-Gal-1) was used in small animal PET imaging and distribution studies to evaluate the specificity of the radiotracer. 124I-αGal-1 PET images showed the immunosuppressive status of the tumor microenvironment, which made it possible to predict resistance to ICB therapy before treatment.

For tumors that were not predicted to respond well to ICB therapy, researchers developed a salvage strategy using a Gal-1 inhibitor, which significantly improved the chances of success.

"Gal-1 PET opens up opportunities for early prediction of ICB efficacy before treatment and facilitates precise design of combination regimens," Liu noted. "This sensitive approach has the potential to achieve individualized precision treatment for patients in the future."