18F FDG PET/CT and Novel Molecular Imaging for Directing Immunotherapy in Cancer.

Immunotherapy has transformed the treatment landscape of many cancers, with durable responses in disease previously associated with a poor prognosis. Patient selection remains a challenge, with predictive biomarkers an urgent unmet clinical need. Current predictive biomarkers, including programmed death-ligand 1 (PD-L1) (measured with immunohistochemistry), are imperfect. Promising biomarkers, including tumor mutation burden and tumor infiltrating lymphocyte density, fail to consistently predict response and have yet to translate to routine clinical practice. Heterogeneity of immune response within and between lesions presents a further challenge where fluorine 18 fluorodeoxyglucose PET/CT has a potential role in assessing response, stratifying treatment, and detecting and monitoring immune-related toxicities. Novel radiopharmaceuticals also present a unique opportunity to define the immune tumor microenvironment to better predict which patients may respond to therapy, for example by means of in vivo whole-body PD-L1 and CD8+ T cell expression imaging. In addition, longitudinal molecular imaging may help further define dynamic changes, particularly in cases of immunotherapy resistance, helping to direct a more personalized therapeutic approach. This review highlights current and emerging applications of molecular imaging to stratify, predict, and monitor molecular dynamics and treatment response in areas of clinical need.