Radiopharmaceuticals as Novel Immune System Tracers

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigms for multiple cancers. However, ICI therapy often fails to generate measurable and sustained antitumor responses, and clinically meaningful benefits remain limited to a small proportion of overall patients. A major obstacle to development and effective application of novel therapeutic regimens is optimized patient selection and response assessment. Noninvasive imaging using novel immunoconjugate radiopharmaceuticals (immuno–positron emission tomography and immuno-single-photon emission computed tomography) can assess for expression of cell surface immune markers, such as programmed cell death protein ligand-1 (PD-L1), akin to a virtual biopsy. This emerging technology has the potential to provide clinicians with a quantitative, specific, real-time evaluation of immunologic responses relative to cancer burden in the body. We discuss the rationale for using noninvasive molecular imaging of the programmed cell death protein-1 and PD-L1 axis as a biomarker for immunotherapy and summarize the current status of preclinical and clinical studies examining PD-L1 immuno–positron emission tomography. The strategies described in this review provide insight for future clinical trials exploring the use of immune checkpoint imaging as a biomarker for both ICI and radiation therapy, and for the rational design of combinatorial therapeutic regimens.