[18F]F-AraG PET Imaging for Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Davis

Must be taking: PD-1, PD-L1 inhibitors

Must not be taking: Nucleoside analogs, Steroids

Disqualifiers: COVID-19, Immunodeficiency, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

8 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop taking my current medications for this trial?

The trial requires that you stop taking certain medications, specifically nucleoside analogs like acyclovir and ganciclovir, before participating. If you are on these medications, you will need to discontinue them at least 7 days before the scan.

What data supports the effectiveness of the treatment [18F]F-AraG for lung cancer?

The use of PET imaging, like [18F]FDG-PET, has been shown to help predict how well lung cancer treatments are working by measuring changes in the tumor early in the treatment process. This suggests that [18F]F-AraG PET imaging might also be useful in evaluating lung cancer treatment responses. ^{1 2 3 4 5}

Is [18F]F-AraG safe for use in humans?

[18F]F-AraG has been studied in healthy volunteers to understand how it spreads in the body and to check its safety. The research provides preliminary safety data, suggesting it is generally safe for human use. ^{6 7 8 9 10}

How does [18F]F-AraG PET Imaging differ from other treatments for lung cancer?

[18F]F-AraG PET Imaging is unique because it uses a specific tracer for PET scans to visualize biological characteristics of lung cancer, potentially offering more detailed information about the tumor compared to standard imaging methods like [18F]FDG-PET/CT. This could help in better understanding tumor behavior and planning personalized treatment strategies. ^{1 3 4 5 11}

Research Team

Simon R Cherry, PhD

Principal Investigator

UC Davis

Eligibility Criteria

This trial is for adults with advanced Non-Small Cell Lung Cancer (NSCLC) who have a tumor larger than 1 cm, not solely in the liver. They must be planning to undergo PD-1 or PD-L1 inhibitor therapy and have an ECOG performance status of ≤2. Healthy volunteers can also join if they weigh less than 240 kg and are willing to use effective contraception during the study.

Inclusion Criteria

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

I am planned to receive treatment targeting PD-1 or PD-L1 for my advanced cancer.

The tumor must be far enough away from certain organs like salivary glands and bladder to accurately measure its size.

Exclusion Criteria

I have had immunotherapy targeting PD-1/PD-L1 for my lung cancer.

My weight is over 529 pounds.

For Healthy subjects: No primary care physician

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo a dynamic [18F]F-AraG PET/CT scan to obtain preliminary data regarding pharmacokinetics and early biodistribution images

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any adverse events 7 days after the scan

1 week

1 visit or call (virtual)

Optional Second Imaging

An optional second dynamic [18F]F-AraG PET/CT scan is performed 7-14 days after the first dose of immunotherapy to explore treatment-related changes

1 day

1 visit (in-person)

Treatment Details

Interventions

• [18F]F-AraG

Trial Overview [18F]F-AraG imaging is being tested using a total body PET/CT scanner on both healthy individuals and NSCLC patients. The goal is to gather preliminary data about how the body processes this substance and how it distributes early on after administration.

Participant Groups

Group I: Non-Small Cell Lung Cancer Patients (NSCLC) Experimental Treatment 1 Intervention

Study participants with NSCLC who are planned to receive PD-1/PD-L1 immunotherapy will undergo a pre-therapy dynamic \[18F\]F-AraG PET/CT scan, and an optional post-therapy (first dose only) dynamic \[18F\]F-AraG PET/CT scan on the uEXPLORER total-body scanner.

Group II: Healthy Volunteers Experimental Treatment 1 Intervention

Study participants will undergo a single dynamic \[18F\]F-AraG PET/CT scan (of duration up to 90-minutes) on the uEXPLORER PET/CT scanner. There will be a follow-up visit or call 7 days after the scan to assess any adverse events that could be attributed to either the scan or the administration of \[18F\]F-AraG.

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

CellSight Technologies, Inc.

Industry Sponsor

Trials

18

Recruited

320+

Findings from Research

[18F]rucaparib, a PET imaging agent developed from the PARP inhibitor rucaparib, effectively visualizes PARP expression in pancreatic cancer models, which could help in selecting patients for rucaparib treatment.

The uptake of [18F]rucaparib is closely linked to PARP1 expression levels, and its binding can be selectively reduced by other PARP inhibitors, indicating its potential for non-invasive imaging and monitoring of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging PARP with [18F]rucaparib in pancreatic cancer models. Chan, CY., Chen, Z., Destro, G., et al.[2023]

[(18)F]FDG-PET imaging is now a standard method for staging non-small-cell lung cancer and can also predict how well a tumor will respond to treatment early on, potentially allowing for personalized therapy adjustments.

By assessing changes in tumor glucose uptake during treatment, [(18)F]FDG-PET may help reduce unnecessary side effects and costs associated with ineffective therapies, improving overall patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of positron emission tomography in the early prediction of response to chemotherapy in patients with non--small-cell lung cancer. Skoura, E., Datseris, IE., Platis, I., et al.[2016]

FDG-PET imaging has significantly improved the assessment and staging of non-small cell lung cancer (NSCLC), leading to a reduction in unnecessary surgeries, as demonstrated by a randomized trial.

The technique not only aids in initial staging but also has prognostic value for evaluating treatment responses and detecting relapses, with ongoing developments in new molecular tracers promising even greater specificity for monitoring cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography in the management of non-small cell lung cancer. Vansteenkiste, JF., Stroobants, SG.[2019]

The use of [18F]FDG-PET/CT is crucial for diagnosing and staging lung cancer, but its limitations have prompted the development of new PET tracers that target specific tumor characteristics.

While no new tracers have yet proven to replace [18F]FDG-PET/CT, they may enhance imaging by providing additional insights into tumor biology and heterogeneity, indicating a promising direction for future lung cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New PET Tracers: Current Knowledge and Perspectives in Lung Cancer. Krarup, MMK., Fischer, BM., Christensen, TN.[2022]

The novel imaging agent [(18)F]F-AraG was successfully synthesized with a radiochemical yield of 7-10%, demonstrating potential for use in positron emission tomography (PET) imaging of T cells.

Preliminary studies indicate that both leukemia cell lines and activated primary thymocytes effectively take up [(18)F]F-AraG, supporting its future application in imaging T-cell activity in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine: a novel agent for imaging T-cell activation with PET. Namavari, M., Chang, YF., Kusler, B., et al.[2021]

The study involving six healthy volunteers demonstrated that the radiolabeled nucleoside analog [18F]F-AraG is well tolerated, with no adverse effects reported after administration, indicating its safety for use in imaging.

Biodistribution results showed that [18F]F-AraG primarily accumulates in the kidneys and liver, aligning with its mechanism of action related to mitochondrial metabolism, making it a promising tracer for various applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution of a Mitochondrial Metabolic Tracer, [18F]F-AraG, in Healthy Volunteers. Levi, J., Duan, H., Yaghoubi, S., et al.[2022]

The PET tracer [18 F]F-AraG is effective for visualizing activated T cells, which could be beneficial in studying various diseases.

A simplified protocol for preparing this PET tracer has been developed, allowing for easier access and use in preclinical research settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simplified and accessible [18 F]F-AraG synthesis procedure for preclinical PET. Högnäsbacka, AA., Cortés González, MA., Halldin, C., et al.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Imaging PARP with [18F]rucaparib in pancreatic cancer models. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Role of positron emission tomography in the early prediction of response to chemotherapy in patients with non--small-cell lung cancer. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Kinetic and Static Analysis of Poly-(Adenosine Diphosphate-Ribose) Polymerase-1-Targeted 18F-Fluorthanatrace PET Images of Ovarian Cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Positron emission tomography in the management of non-small cell lung cancer. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

New PET Tracers: Current Knowledge and Perspectives in Lung Cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Synthesis of 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine: a novel agent for imaging T-cell activation with PET. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Biodistribution of a Mitochondrial Metabolic Tracer, [18F]F-AraG, in Healthy Volunteers. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Disposition of 9-beta-D-arabinofuranosyl-2-fluoroadenine in mice, dogs, and monkeys. [2014]

9. England pubmed.ncbi.nlm.nih.gov

Simplified and accessible [18 F]F-AraG synthesis procedure for preclinical PET. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Differential metabolism of 9-beta-D-arabinofuranosylguanine in human leukemic cells. [2014]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of [18F]AlF-EMP-105 for Molecular Imaging of C-Met. [2023]