[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

Trial Summary

What is the purpose of this trial?

This pilot study aims to evaluate the test-retest variability of \[18F\]F-AraG-PET imaging in patients with advanced NSCLC tumors. The main objectives of the study are to quantify the uptake of \[18F\]F-AraG in tumors and lymphoid tissue in two consecutive scans spaced not longer than 7 days apart from each other to estimate the magnitude of physiologic and measurement variability. To explore these objectives, eligible subjects will undergo two \[18F\]F-AraG PET/CT scans within 7 days of each other prior to receiving treatment. This study is a single-site, open-label, non-randomized, single-arm pilot trial. Patients and care providers will not be blinded to any part of the study.

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

The use of PET scans with similar tracers like [(18)F]FDG has shown promise in predicting how well lung cancer responds to treatment early on, which can help tailor therapy to individual patients and potentially reduce side effects and costs. ^{1 2 3 4 5}

Is [18F]F-AraG safe for 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 included preliminary safety assessments, suggesting it is generally safe for human use. ^{6 7 8 9 10}

How does the [18F]F-AraG PET scan treatment differ from other lung cancer treatments?

The [18F]F-AraG PET scan is unique because it uses a novel tracer for imaging, which may provide more specific information about the biological characteristics of lung cancer compared to the standard [18F]FDG-PET scans. This could potentially improve the accuracy of diagnosis, staging, and treatment planning by targeting different aspects of tumor biology beyond glucose metabolism. ^{1 2 11 12 13}

Research Team

Muhammad Furqan

Principal Investigator

Holden Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

[(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]

[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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. 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]

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

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

3. Germany pubmed.ncbi.nlm.nih.gov

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

4. United States 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. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

7. 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]

8. Germany pubmed.ncbi.nlm.nih.gov

Influx rate of 18F-fluoroaminosuberic acid reflects cystine/glutamate antiporter expression in tumour xenografts. [2023]

9. Greece pubmed.ncbi.nlm.nih.gov

Development and pre-clinical evaluation of new 68Ga-NOTA-folate conjugates for PET imaging of folate receptor-positive tumors. [2019]

10. England pubmed.ncbi.nlm.nih.gov

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

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

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

12. England pubmed.ncbi.nlm.nih.gov

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

13. Switzerland pubmed.ncbi.nlm.nih.gov

Positron emission tomography imaging of lung cancer: An overview of alternative positron emission tomography tracers beyond F18 fluorodeoxyglucose. [2022]