Imaging Advanced NSCLC Patients Undergoing PD-1/PD-L1 Directed Therapy Using [18F]-FARAG

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.