Imaging for Lung Cancer

Overseen By Amy Mundisev

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CellSight Technologies, Inc.

Must be taking: Checkpoint inhibitors

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: 1

Duration: 12 months

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

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 study looked at the radiation levels and found it to be safe for use in humans. ^{1 2 3 4 5}

What makes the drug [18F]F-AraG unique for lung cancer imaging?

[18F]F-AraG is unique because it is a novel PET imaging agent specifically designed to visualize T-cell activation, which could provide more detailed insights into the immune response in lung cancer compared to traditional imaging agents like [18F]FDG that focus on glucose metabolism. ^{1 3 5 6 7}

What is the purpose of this trial?

This pilot study uses \[18F\]F AraG PET imaging to evaluate the immunological response to checkpoint inhibitor therapy (CkIT) in patients with advanced NSCLC tumors. The study's main objectives are to quantify the change in \[18F\]F AraG PET signal before and while on CkIT therapy and to correlate this change in \[18F\]F AraG PET signal with radiographic response. To explore these objectives, eligible subjects will undergo pre- and on - CkIT treatment \[18F\]F AraG PET/CT scans, and will be followed up for 12 months for assessment of radiographic and clinical outcomes. 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.

Research Team

Muhammad Furqan

Principal Investigator

Holden Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) who are about to start immunotherapy. They should be able to perform daily activities with ease or with some limitations (ECOG status 0, 1, or 2). Participants must also agree to follow-up visits at the University of Iowa.

Inclusion Criteria

I can take care of myself and perform daily activities.

Participants consent to be monitored at the University of Iowa.

My cancer can be measured by tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Imaging

Participants undergo pre-treatment [18F]F AraG PET/CT scans to evaluate baseline T-cell activation

1 week

1 visit (in-person)

Treatment

Participants receive PD-1/PD-L1 directed therapy and undergo on-treatment [18F]F AraG PET/CT scans

12 months

Multiple visits (in-person) for therapy and imaging

Follow-up

Participants are monitored for radiographic and clinical outcomes after treatment

12 months

Treatment Details

Interventions

• [18F]F-AraG

Trial Overview [18F]F-AraG PET imaging is being tested in this study to see how well it shows the body's immune response to checkpoint inhibitor therapy in NSCLC patients. The trial involves scans before and during treatment, followed by a year-long observation period.

Participant Groups

Group I: Advanced non small cell lung cancer (NSCLC) patients undergoing PD-1/PD-L1 directed therapy Experimental Treatment 1 Intervention

[18F]F-AraG is already approved in United States for the following indications:

Approved in United States as Nelarabine (prodrug of AraG) for:

• T-cell acute lymphoblastic leukemia
• T-cell lymphoblastic lymphoma

Who Is Running the Clinical Trial?

CellSight Technologies, Inc.

Lead Sponsor

Trials

18

Recruited

320+

Findings from Research

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 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 evaluated two thymidine analogs, FAU and FMAU, as potential PET imaging agents in SCID mice with human T-cell leukemia, showing that FMAU accumulates significantly in tumor tissue and incorporates into tumor DNA more effectively than FAU or thymidine.

FMAU demonstrated a higher concentration in tumor DNA, being 45% greater than thymidine and threefold greater than FAU, suggesting its potential as a functional PET imaging agent for tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiolabeled 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU) and 2'-fluoro-5-methyldeoxyuracil-beta -D-arabinofuranoside (FMAU) as tumor-imaging agents in mice. Wang, H., Oliver, P., Nan, L., et al.[2020]

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 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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

Radiolabeled 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU) and 2'-fluoro-5-methyldeoxyuracil-beta -D-arabinofuranoside (FMAU) as tumor-imaging agents in mice. [2020]

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

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

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

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

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

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