PET Imaging of Cancer Immunotherapy

Immune system activation can be elicited in viral infections, active immunization, or cancer immunotherapy, leading to the final common phenotype of increased glycolytic use by immune cells and subsequent detection by 18F-FDG PET. Because 18F-FDG is also used in baseline staging PET/CT scans and in tumor response assessment, physicians are faced with a unique challenge when evaluating tumor response in patients receiving cancer immunotherapy. The burgeoning field of cancer immunotherapy and the paucity of PET probes that can reliably differentiate activated immune cells from metabolically active cancer cells underscore the pressing need to identify and develop additional molecular imaging strategies. In an effort to address this concern, investigators have taken several molecular imaging approaches for cancer immunotherapy. Direct ex vivo labeling of T lymphocytes with radioactive probes before reinfusion represents the earliest attempts but has proven to be clinically limited because of significant PET probe dilution from proliferation of activated immune cells. Another approach is the indirect in vivo labeling of immune cells via PET reporter gene expression and involves the ex vivo genetic engineering of T lymphocytes with a reporter gene, reinfusion into the host, and the subsequent use of a PET probe specific for the reporter gene. The most recent approach involves the direct in vivo labeling of immune cells by targeting endogenous immune cell biochemical pathways that are differentially expressed during activation. In conclusion, these novel PET-based imaging approaches have demonstrated promise toward the goal of in vivo, noninvasive immune monitoring strategies for evaluating cancer immunotherapy.