[18F]F-AraG/Total Body PET Imaging and Healthy Subjects and Lung Cancer Patients

A Pilot Study of [18F]F-AraG Pharmacokinetics in Tumors and Non-Malignant Tissue Using Dynamic Total Body PET Imaging in Healthy Subjects and in Patients With Non-Small Cell Lung Cancer (NSCLC)

In this pilot study, healthy volunteers and patients with Non-Small Cell Lung Cancer will undergo [18F]F-AraG dynamic imaging on the uEXPLORER total body Positron Emission Tomography/Computerized Tomography scanner to obtain preliminary data regarding pharmacokinetics and early biodistribution images.

[18F]F-AraG, a fluorine-18 labeled analog of an FDA approved drug (Nelarabine) is a new imaging tracer targeted at imaging activated T-cells. Given that immunotherapeutic strategies, in particular immune checkpoint antibodies, focus on the generation of T-cell-based antitumor immunity, uptake of [18F]F-AraG within the tumor is hypothesized to correlate with T-cell mediated immune response seen in the biopsy samples of cancer patients treated with immune checkpoint blockade. Correlation of pre- and post-treatment intratumoral immune infiltration by means of PET imaging will guide the development of future clinical trials investigating the role of [18F]F-AraG in the monitoring of anti-tumor immune responses. Therefore, proper quantification of [18F]F-AraG uptake in tumor lesions, and understanding its relation with physiologic uptake in background tissues is important. Note: checkpoint therapy in this study is standard-of-care and is not under investigation.

Available PET/CT scanners can obtain dynamic images only on a portion of the body as large as their axial field of view, generally anywhere between 15-30 cm. The 194 cm long uEXPLORER total-body PET scanner is the world's first device to offer the ability to tomographically image all parts of the body simultaneously. Thus, the uEXPLORER PET/CT (now commercially available and with FDA 510(k) clearance) is the only scanner in the world capable of acquiring total-body dynamic images.

In this pilot study, 2-4 healthy volunteers will undergo [18F]F-AraG dynamic imaging on the uEXPLORER total body PET/CT scanner to obtain preliminary data regarding pharmacokinetics and early biodistribution images. In addition, 2-4 patients with NSCLC and planned for standard-of-care PD-1/PD-L1 immunotherapy will undergo [18F]F-AraG dynamic imaging similarly on the uEXPLORER total body PET/CT scanner to obtain data regarding pharmacokinetics of the tracer in tumor lesions in the context of normal tissue uptake. An optional second similar scan will be performed 7-14 days after the first dose of immunotherapy to explore and document any treatment related changes in [18F]F-AraG uptake and kinetics.

The study and data collected will be important to recommend an ideal time to acquire a whole body static scan using conventional and widely available PET/CT scanners for adequate tumor to background contrast and quantification, which in turn, will be essential for further clinical development of [18F]F-AraG to aid the monitoring of anti tumor immune responses.

Inclusion Criteria:

1. Age ≥ 18 years.

2. Ability to understand the purposes and risks of the trial and has signed an IRB-approved informed consent form.

3. Willingness and ability to comply with all protocol required procedures.

4. For men and women of child-producing potential, willingness to use of effective double barrier contraceptive methods during the study, up to 1 day after the last administration of the investigational product.

   For NSCLC subjects only:

5. Patients with histologically confirmed advanced, locally advanced, or localized NSCLC.

6. Planned to undergo treatment with a PD-1 or PD-L1 inhibitor either as 1) monotherapy or as combination therapy with concurrent chemotherapy as treatment for advanced/metastatic disease; 2) As consolidation therapy following chemoradiation for locally advanced disease or 3) As induction therapy either as monotherapy or combination therapy with chemotherapy prior to planned surgical resection

7. At least 1 tumor lesion > 1 cm (cannot be only in liver) documented on CT or MRI or FDG-PET/CT (RECIST criteria 1.1; >1.5 cm for nodal lesions) within 45 days prior to scan date.

8. Per investigator's assessment and in consultation with oncologists, at least one eligible lesion must be sufficiently separated from tissues with known high [18F]F-AraG uptake, such as salivary glands, bladder, liver and kidneys so that quantification will be feasible.

9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

10. Meeting all clinical safety lab values per institution's standard of care, or Investigator's discretion, for patients receiving cancer treatment.

Exclusion Criteria:

Subjects are not eligible if they meet ANY of the following criteria:

1. Serious comorbidities (nonmalignant disease or other conditions) that in the opinion of the investigator could compromise protocol objectives.

2. History of recent COVID-19 infection within the last 2 months OR history of COVID requiring hospitalization with lung injury at Investigator's discretion

3. Subjects with a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the scan

4. Subjects receiving therapy with nucleoside analogs including but not limited to: acyclovir, valaclovir, penciclovir, famciclovir, ganciclovir, ribavirin, valganciclovir, glanciclovir

5. Pregnant women or nursing mothers.

6. Body weight more than 240 kg (529 pounds)

   For NSCLC subjects only:

7. Prior Treatment with anti-PD-1/PD-L1 immunotherapy.

   For Healthy subjects

8. No primary care physician