Imaging of T-cell Activation With [18F]F-araG in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Undergoing PD-1/PD-L1 Directed Therapy

Checkpoint inhibitor therapy has led to impressive clinical successes, providing objective and durable responses in patients with advanced cancers that previously had 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 evaluating complex immunologic processes within the body.

[18F]F-AraG was developed as an agent for imaging activated T cells. [18F]F-AraG is an 18F-labeled analog of 9-b-D-Arabinofuranosylguanine a compound that has shown selective accumulation in T cells and whose prodrug, nelarabine, is FDA-approved for the 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. Additionally, in vivo whole-body imaging of activated T cells can provide critical information about the effect of immunomodulation in resulting in autoimmunity, and thus help predict adverse events of immunotherapy.

To sum up, characterizing the immune system alterations in vivo, in real-time, and non-invasively using PET imaging may enable us to predict better which patients will benefit from which Checkpoint Inhibitor Therapy (CkIT) treatment regimen.