[18F]F-AraG PET Scan Reliability for Lung Cancer

Overseen By Amy Mundisev

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CellSight Technologies, Inc.

Disqualifiers: Pregnancy, Nursing, Claustrophobia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 2

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the reliability of a new imaging technique called [18F]F-AraG-PET in detecting changes in advanced non-small cell lung cancer (NSCLC). The goal is to assess the consistency of the scans in identifying cancer activity by conducting two scans within a week before any treatment begins. The study is small and straightforward, with full transparency for participants. Suitable candidates have advanced NSCLC, are about to start immunotherapy, and do not suffer from severe claustrophobia. As a Phase 2 trial, this research measures the effectiveness of the imaging technique in an initial, smaller group of participants.

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

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the [18F]F-AraG PET scan is safe for patients with advanced NSCLC?

A previous study used [18F]F-AraG to observe how the body processes this imaging agent, and the results showed that patients tolerated it well. Another study examined its role in detecting T-cell activation, a key part of the immune system's response, and also found [18F]F-AraG safe to use.

Now in a Phase 2 trial for this specific purpose, [18F]F-AraG has already passed initial safety tests. This phase focuses more on the treatment's effectiveness, but safety remains under close observation. Previous studies suggest it is generally safe for use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the [18F]F-AraG PET scan because it offers a new way to visualize the immune system's activity in lung cancer patients. Unlike traditional imaging methods like CT or MRI scans, which focus on tumor size and structure, [18F]F-AraG targets activated T-cells, which are crucial for the body's immune response against cancer. This approach might give doctors a clearer picture of how well a patient's immune system is responding to treatment, potentially leading to more personalized and effective care strategies for advanced non-small cell lung cancer.

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

Research has shown that [18F]F-AraG is being studied to image T-cells, which play a crucial role in fighting cancer. In this trial, patients with non-small cell lung cancer (NSCLC) will undergo two [18F]F-AraG PET/CT scans within 7 days of each other before treatment. Studies have found that [18F]F-AraG can help visualize how these cells move and gather in the body, particularly in NSCLC patients. This imaging tool has tracked T-cell activity, which is essential for understanding the body's response to treatments. Early results suggest that [18F]F-AraG can effectively monitor these immune cells, aiding doctors in assessing cancer progression and treatment efficacy. Although still under investigation, these findings indicate it could be a valuable tool in cancer management. ^{2 6 7 8 9}

Who Is on the Research Team?

Muhammad Furqan

Principal Investigator

Holden Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-small cell lung cancer (NSCLC) who are candidates for immunotherapy. They should have measurable disease and be in a relatively stable condition, as indicated by an ECOG performance status of 0 to 2. Pregnant or nursing women, individuals with severe claustrophobia, or those with serious health issues that could interfere with the study cannot participate.

Inclusion Criteria

My cancer can be measured by tests.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

You have a strong fear of small, enclosed spaces.

Serious comorbidities that in the opinion of the investigator/sponsor could compromise protocol objectives

Pregnant women or nursing mothers

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Imaging

Participants undergo two [18F]F-AraG PET/CT scans to evaluate test-retest variability

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [18F]F-AraG

Trial Overview

[18F]F-AraG PET imaging is being tested to see how consistent it is when used twice within a week on patients with advanced NSCLC. The goal is to measure how much [18F]F-AraG builds up in tumors and immune system tissues before treatment starts. This single-site pilot trial involves two scans without any blinding.

How Is the Trial Designed?

Group I: Advanced non small cell lung cancer (NSCLC) patients Experimental Treatment 1 Intervention

Patients will undergo two \[18F\]F AraG PET/CT scans within 7 days of each other prior to receiving treatment

Who Is Running the Clinical Trial?

CellSight Technologies, Inc.

Lead Sponsor

Trials

18

Recruited

320+

University of Iowa Hospitals & Clinics

Collaborator

Trials

1

Recruited

10+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

Published Research Related to This Trial

The newly developed 68Ga-NOTA-folate conjugate shows high radiochemical yields (over 95%) and purity (over 98%) in under 20 minutes, making it a rapid and efficient method for preparing folate radiotracers for cancer detection.

In vivo studies demonstrated that the 68Ga-NOTA-folate conjugate effectively targets folate receptor-positive tumors, with significant uptake in human cancer xenografts, indicating its potential as a molecular probe for diagnosing and monitoring cancers like ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and pre-clinical evaluation of new 68Ga-NOTA-folate conjugates for PET imaging of folate receptor-positive tumors. Aljammaz, I., Al-Otaibi, B., Al-Hokbany, N., et al.[2019]

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]

[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 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 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 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]

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 study successfully synthesized the first 18F-labelled ATM inhibitor, which allows for non-invasive imaging of ATM protein and tracking of the drug's pharmacokinetics, potentially aiding in personalized cancer treatment.

In vitro and in vivo evaluations showed that while the uptake of the 18F-labelled inhibitor was specific to ATM and could be blocked by known ATM inhibitors, its retention in cells decreased over time, indicating some limitations in its effectiveness for imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent. Fraser, CR., Ajenjo, J., Veal, M., et al.[2023]

The new tracer 18F-fluoroaminosuberic acid (18F-FASu) shows higher early uptake in tumors compared to the conventional tracer 18F-fluorodeoxyglucose (18F-FDG), indicating its potential for better tumor assessment in PET imaging.

The influx rate of 18F-FASu is significantly correlated with the expression of the cystine/glutamate antiporter (xCT), suggesting that 18F-FASu uptake may be influenced by the tumor's oxidative stress levels, which could enhance its utility in evaluating tumor biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influx rate of 18F-fluoroaminosuberic acid reflects cystine/glutamate antiporter expression in tumour xenografts. Pitman, KE., Alluri, SR., Kristian, A., et al.[2023]

FDG-PET imaging has become an important tool for diagnosing and staging non-small cell lung cancer, gaining acceptance and reimbursement in many European countries over the past five years.

Further validation through large-scale studies is needed to confirm the effectiveness of FDG-PET in improving treatment outcomes, survival rates, and cost-effectiveness in lung cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of positron emission tomography with 18F-fluoro-2-deoxy-D-glucose in respiratory oncology. Vansteenkiste, JF., Stroobants, SG.[2019]

In a study of 125 non-small cell lung cancer patients treated with erlotinib, the presence of new lesions on (18)F-FDG PET scans taken 2 weeks into treatment was found to be a significant predictor of overall survival.

The study also highlighted that while a reduction in maximum standardized uptake value (SUV) could indicate better survival, this was only true when not considering the patient's EGFR mutation status, suggesting that mutation status plays a crucial role in interpreting PET results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FDG PET as a surrogate biomarker in non-small cell lung cancer treated with erlotinib: newly identified lesions are more informative than standardized uptake value. Bengtsson, T., Hicks, RJ., Peterson, A., et al.[2022]

[(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]

Lung cancer remains the leading cause of cancer-related deaths in China, and PET/CT imaging using the 18F-FDG tracer is crucial for diagnosing and staging the disease by monitoring glucose metabolism in tumors.

Recent advancements have led to the development of novel PET tracers that target various biological characteristics of lung cancer, such as cellular proliferation and tumor hypoxia, which may enhance diagnostic accuracy and treatment planning beyond traditional glucose metabolism assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography imaging of lung cancer: An overview of alternative positron emission tomography tracers beyond F18 fluorodeoxyglucose. Zhu, J., Pan, F., Cai, H., et al.[2022]

Citations

1.

withpower.com

withpower.com/trial/18ff-arag-pet-scan-reliability-for-lung-cancer-a3eff

[18F]F-AraG PET Scan Reliability for Lung Cancer

This pilot study aims to evaluate the test-retest variability of \[18F\]F-AraG-PET imaging in patients with advanced NSCLC tumors.

2.

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 ...

3.

pubmed.ncbi.nlm.nih.gov

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

Total-body Dynamic Imaging and Kinetic Modeling of 18 F ...

The aim of this study was to obtain preliminary data on total-body pharmacokinetics of 18F-AraG, as a potential quantitative biomarker for ...

4.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT04052412

Biodistribution and Kinetics of 18F-AraG in Non-Small Cell ...

This study is to assess the biodistribution and kinetics of a novel T-cell imaging agent in non-small cell lung cancer patients undergoing immunotherapy ...

5.

link.springer.com

link.springer.com/article/10.1007/s00259-024-06931-3

Pharmacokinetic analysis and simplified uptake measures ...

The aim of this study was to determine the optimal pharmacokinetic model to quantify tumour lesion [ 18 F]F-AraG uptake in patients with non-small cell lung ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04726215

NCT04726215 | Imaging of T-cell Activation With [18F]F- ...

This is a pilot study using [18F]F AraG PET imaging to evaluate the immunological response to checkpoint inhibitor therapy (CkIT) in patients with advanced ...

7.

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 ...

8.

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 ...

9.

researchgate.net

researchgate.net/publication/46256837_Synthesis_of_2'-Deoxy-2'-18FFluoro-9-b-D-Arabinofuranosylguanine_a_Novel_Agent_for_Imaging_T-Cell_Activation_with_PET

Deoxy-2′-[18F]Fluoro-9-β-D-Arabinofuranosylguanine: a ...

9-(β-D-Arabinofuranosyl)guanine (AraG) is a guanosine analog that has a proven efficacy in the treatment of T-cell lymphoblastic disease.