Test-retest Evaluation of [18F]F-AraG PET

Checkpoint inhibitor therapy has led to impressive clinical successes, providing objective and durable responses in patients with advanced cancers that previously had very few treatment options. Unfortunately, immunotherapy works only in a relatively small fraction of patients with solid tumors. The current standard of care anatomic imaging adequately assessed treatment efficacy in the pre-immunotherapy era, when tumor volume burden directly correlated with clinical outcomes. However, anatomic imaging is found to be limited due to the cellular and molecular nature of early responses to immunotherapy. PET imaging is a sensitive technique that uses radiolabeled agents to visualize the distribution of specific molecular targets in the body. Based on its ability to pinpoint molecular activity, PET imaging agents that target key players of the immune response could offer a powerful noninvasive tool for evaluation of complex immunologic processes within the body. \[18F\]F-AraG was developed as an agent for imaging activated T cells (Namavari et al., 2011)). \[18F\]F-AraG is a 18F-labeled analog of 9-b-D-Arabinofuranosylguanine a compound that has shown selective accumulation in T cells (Eriksson, et al., 1994) and whose prodrug, nelarabine, is FDA-approved for treatment of patients with T cell acute lymphoblastic leukemia and T cell lymphoblastic lymphoma. \[18F\]F-AraG is independent of the type of immunotherapy regimen being administered adoptive cell therapy, checkpoint inhibitors, cancer vaccines or a combination of immunotherapy and conventional medicines. In vivo, real time imaging of activated T cells in solid tumors before and at a timepoint during and after CkIT therapy can help understand the effects of checkpoint blockade therapy. Repeatability, as an estimate of the magnitude of change that distinguishes normal physiologic and measurement variability from true biologic change, is important to interpreting changes encountered on PET scans in the response-to-treatment setting. This study will establish test-retest variability of \[18F\]F-AraG uptake in tumors (primary and metastatic sites) and lymphoid tissue in NSCLC patients prior to start of therapy. The results lead to a better understanding of the parameters affecting signal quantitation.