[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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to gather early data on a new imaging method using [18F]F-AraG, an imaging agent, to better understand lung cancer, specifically Non-Small Cell Lung Cancer (NSCLC). Researchers will use a special PET/CT scanner to observe how the imaging agent moves and spreads in the body. The trial includes two groups: healthy volunteers and those with NSCLC who are about to start certain immune therapies. Eligible participants must have NSCLC, be scheduled for PD-1/PD-L1 therapy, and have a tumor confirmed by recent imaging. As an Early Phase 1 trial, this research focuses on understanding how this new imaging method works in people, offering participants a chance to contribute to groundbreaking advancements in lung cancer diagnostics.

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 prior data suggests that [18F]F-AraG PET imaging is safe for humans?

Research shows that [18F]F-AraG is being tested as a new imaging tool to observe the immune system's response to certain cancer treatments. In earlier studies, patients tolerated [18F]F-AraG well, with no serious side effects reported, suggesting it is generally safe for imaging use.

However, this trial remains in an early stage, with researchers still gathering initial safety data. The focus is on understanding how the body processes the treatment. If [18F]F-AraG were unsafe, the trial would not have continued. Yet, because it is still early, the long-term effects remain unknown. Participants in the study will be closely monitored for any side effects after the scan. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the [18F]F-AraG PET imaging technique for lung cancer because it offers a fresh approach to evaluating how well the immune system is engaging with cancer cells. Unlike traditional imaging methods that might not clearly show immune activity, [18F]F-AraG is a radiotracer specifically designed to highlight active T-cells, which are crucial in fighting cancer. This provides a more precise picture of how treatments like PD-1/PD-L1 immunotherapy are working in non-small cell lung cancer (NSCLC) patients. By potentially offering earlier insights into treatment effectiveness, this imaging technique could help tailor therapies more quickly and effectively, improving patient outcomes.

What evidence suggests that [18F]F-AraG PET imaging is effective for lung cancer?

Research has shown that [18F]F-AraG is under study for its potential to detect T-cell activity in non-small cell lung cancer (NSCLC). T-cells, a type of immune cell, help fight cancer. In this trial, participants with NSCLC will undergo [18F]F-AraG PET imaging to assess T-cell activity before and optionally after receiving PD-1/PD-L1 immunotherapy. Studies suggest that [18F]F-AraG PET imaging might effectively measure T-cell activity in the body. Early findings indicate that this imaging technique could help assess the immune response in NSCLC patients, offering a non-invasive method to understand how the body is combating cancer. This could be crucial for customizing treatments and monitoring their effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Simon R Cherry, PhD

Principal Investigator

UC Davis

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

[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]

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]

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]

[(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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04726215

NCT04726215 | Imaging of T-cell Activation With [18F]F- ... Imaging of T-cell Activation With [18F]F-AraG in Advanced Non Small Cell Lung Cancer ... This is a pilot study using [18F]F AraG PET imaging to evaluate ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39448270/

[18F]F-AraG Uptake in Vertebral Bone Marrow May Predict ... The aim of this study was to assess the value of [18F]F-AraG PET imaging as a noninvasive method for evaluation of system-wide immune status of ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/early/2024/08/01/jnumed.123.267003

Total-Body Dynamic Imaging and Kinetic Modeling of [18F]F ... The aim of this study was to obtain preliminary data on total-body pharmacokinetics of [18F]F-AraG as a potential quantitative biomarker for ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04186988?term=AREA%5BInterventionSearch%5D(%229-arabinofuranosylguanine%22)&rank=1

[18F]-AraG for the Detection of T-Cell Activation in ... This trial studies how well [18F]-AraG works in detecting T-cell activation in patients with non-small cell lung cancer that has spread to other places in the ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37790461/

Total-body Dynamic Imaging and Kinetic Modeling of 18 F ... Our findings highlight the promise of 18 F-AraG dynamic imaging as a non-invasive biomarker for quantifying the immune response to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11372257/

Total-Body Dynamic Imaging and Kinetic Modeling of [18F] ... This study introduces [ 18 F]F-AraG dynamic imaging and kinetic modeling as a noninvasive quantitative biomarker for evaluating the immune response to ...

7. ctv.veeva.com ctv.veeva.com/study/pet-imaging-with-18f-f-arag-in-advanced-non-small-cell-lung-cancer-nsclc

PET Imaging With [18F]F-AraG in Advanced Non-small Cell ... The purpose of this study is to find out how the radiotracer called [18F]F-AraG can help investigate changes in cancer's anti-tumor immune ...