18F-FAZA PET Scan for Lung Cancer

Overseen By Stephen Breen, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Previous radiotherapy, Previous systemic therapy, Active malignancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

20 Participants Needed

Trial Summary

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

The trial protocol does not specify whether you need to stop taking your current medications. However, it does allow for concurrent systemic therapy, which suggests you may be able to continue some treatments.

What data supports the effectiveness of the drug 18F-FAZA for lung cancer?

Research shows that 18F-FAZA is effective in identifying low-oxygen areas within tumors, which is important for diagnosing and treating cancer. It has good image contrast and is used in PET scans to help doctors see these hypoxic regions clearly. ^{1 2 3 4 5}

Is 18F-FAZA safe for use in humans?

Research indicates that a 370-MBq injection of 18F-FAZA is safe for clinical use, with radiation doses similar to other commonly used PET tracers. The highest radiation exposure is to the bladder wall, but overall, the effective dose is comparable to other hypoxia tracers. ^{1 2 4 5 6}

How does the drug 18F-FAZA differ from other lung cancer treatments?

18F-FAZA is unique because it is a PET scan tracer specifically designed to identify hypoxic (low oxygen) regions within tumors, which can be crucial for understanding tumor behavior and planning treatment. Unlike other treatments that may target cancer cells directly, 18F-FAZA helps visualize areas of the tumor that are not getting enough oxygen, providing valuable information for treatment planning. ^{1 2 4 5 7}

What is the purpose of this trial?

This trial uses a special scan with a special substance to find low oxygen levels in lung cancer tumors. It targets lung cancer patients about to start treatment. The special substance highlights low-oxygen areas in the tumor, helping doctors understand the tumor better. The special substance has been used in various studies to evaluate low oxygen areas within tumors.

Research Team

Alex Sun, MD, FRCPC

Principal Investigator

The Princess Margaret Cancer Foundation

Eligibility Criteria

This trial is for adults over 18 with stage II or III lung cancer who are set to receive radiotherapy. It's open to those with both non-small cell (NSCLC) and small cell lung cancer (SCLC), even if they're getting other treatments too. Women must test negative for pregnancy before the PET scan, and all participants need to be able to lie on their back for an hour and give written consent.

Inclusion Criteria

Concurrent systemic therapy allowed

Ability to provide written informed consent to participate in the study

You have stage II or III lung cancer and may need radiation therapy for the main tumor or nearby lymph nodes.

Exclusion Criteria

Failure to provide written informed consent

Pregnancy

You have received radiation therapy to the areas where the treatment will be given.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive a FAZA PET Scan to measure hypoxia in the tumor

1 day

1 visit (in-person)

Radiotherapy

Participants undergo radiotherapy treatment following the PET scan

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 18-F-FAZA

Trial Overview The study tests a PET scan using a tracer called FAZA that detects low oxygen levels in tumors, which can affect how well cancer responds to treatment. Participants will have one FAZA PET scan before starting radiotherapy, aiming to see if this method offers better insights into tumor hypoxia than current techniques.

Participant Groups

Group I: 18-F-FAZA Scan Experimental Treatment 1 Intervention

All patients enrolled in this study will receive a FAZA PET Scan prior to their first radiation therapy fraction

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

The study identified the reversible two-tissue compartment model with blood volume parameter (2T4k+VB) as the best method for analyzing the kinetics of the PET tracer [(18)F]FAZA in non-small cell lung cancer patients, based on dynamic scans from nine participants.

It was found that using image-derived plasma input functions (IDIF) with venous blood samples can effectively replace traditional arterial blood sampling for analyzing [(18)F]FAZA studies, simplifying the process without compromising accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic analysis of [18F]FAZA in non-small cell lung cancer patients. Verwer, EE., van Velden, FH., Bahce, I., et al.[2021]

In a pilot study involving 11 patients with laryngeal squamous cell carcinoma, (18)F-FAZA-PET/CT scans detected hypoxic regions in 9 out of 11 tumors, indicating its potential utility in identifying tumor hypoxia.

However, the study found no clear correlation between (18)F-FAZA uptake and established hypoxia markers, suggesting that further research is needed to validate the accuracy of (18)F-FAZA-PET for guiding radiotherapy planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of hypoxic subvolumes in laryngeal cancer with (18)F-fluoroazomycinarabinoside ((18)F-FAZA)-PET/CT scanning and immunohistochemistry. Bruine de Bruin, L., Bollineni, VR., Wachters, JE., et al.[2019]

The newly developed radiolabeled azomycin-2'-deoxyriboside ([18F]FAZDR) demonstrated significantly higher tumor contrast in PET imaging compared to the existing [18F]FAZA, particularly at earlier time points after injection, indicating its potential for improved imaging of hypoxia in tumors.

[18F]FAZDR showed a unique response to oxygen levels, with tracer uptake in tumors inversely correlating with oxygen breathing, suggesting that it may provide more mechanistic insights into tumor hypoxia compared to [18F]FAZA, which relies solely on passive diffusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]Fluoro-azomycin-2´-deoxy-β-d-ribofuranoside - A new imaging agent for tumor hypoxia in comparison with [18F]FAZA. Schweifer, A., Maier, F., Ehrlichmann, W., et al.[2017]

In a study involving 10 patients with advanced non-small cell lung cancer, the relationship between tumor blood flow (TBF) and the uptake of the PET tracer (18)F-FAZA was explored, revealing that decreased TBF does not always correlate with lower (18)F-FAZA uptake, indicating a more complex interaction than previously thought.

The findings suggest that areas of high (18)F-FAZA uptake can exist alongside high TBF, challenging the assumption that hypoxia (indicated by (18)F-FAZA uptake) is solely linked to low perfusion, and highlighting the importance of multiparametric analysis in understanding tumor biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with ¹⁸F-Fluoroazomycin Arabinoside and ¹⁵O-H₂O PET. Iqbal, R., Kramer, GM., Verwer, EE., et al.[2017]

The novel azomycin nucleosides beta-2-FAZA and beta-3-FAZL were synthesized and showed similar radiosensitization properties to the existing PET tracer FAZA, with sensitizer enhancement ratios of about 1.8 in HCT-116 cancer cells.

These new compounds have slightly lower partition coefficients than FAZA, which may influence their uptake and effectiveness in imaging tumor hypoxia, potentially improving the diagnosis and treatment of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and hypoxia selective radiosensitization potential of beta-2-FAZA and beta-3-FAZL: fluorinated azomycin beta-nucleosides. Kumar, P., Emami, S., Kresolek, Z., et al.[2019]

The phase I study involving five patients with non-small cell lung cancer demonstrated that 18F-FAZA is safe for clinical use, with effective radiation doses comparable to other commonly used PET tracers, indicating its potential for noninvasive tumor hypoxia identification.

The biodistribution of 18F-FAZA showed significant uptake in muscle and liver, with the urinary bladder wall receiving the highest radiation dose, suggesting careful consideration of organ exposure during its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Evaluation of PET-Based Human Biodistribution and Dosimetry of 18F-FAZA, a Tracer for Imaging Tumor Hypoxia. Savi, A., Incerti, E., Fallanca, F., et al.[2018]

In a study involving 9 non-small cell lung cancer patients, both Logan graphic analysis and spectral analysis provided highly accurate quantifications of (18)F-FAZA uptake, correlating well with traditional nonlinear regression methods.

The study found that while tumor-to-blood ratios (SUVr) were comparable, they exhibited significant bias at high volumes of distribution, suggesting that parametric methods may be more reliable for precise hypoxia imaging in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parametric methods for quantification of 18F-FAZA kinetics in non-small cell lung cancer patients. Verwer, EE., Bahce, I., van Velden, FH., et al.[2017]

References

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

Pharmacokinetic analysis of [18F]FAZA in non-small cell lung cancer patients. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Assessment of hypoxic subvolumes in laryngeal cancer with (18)F-fluoroazomycinarabinoside ((18)F-FAZA)-PET/CT scanning and immunohistochemistry. [2019]

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

[18F]Fluoro-azomycin-2´-deoxy-β-d-ribofuranoside - A new imaging agent for tumor hypoxia in comparison with [18F]FAZA. [2017]

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

Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with ¹⁸F-Fluoroazomycin Arabinoside and ¹⁵O-H₂O PET. [2017]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Synthesis and hypoxia selective radiosensitization potential of beta-2-FAZA and beta-3-FAZL: fluorinated azomycin beta-nucleosides. [2019]

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

First Evaluation of PET-Based Human Biodistribution and Dosimetry of 18F-FAZA, a Tracer for Imaging Tumor Hypoxia. [2018]

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

Parametric methods for quantification of 18F-FAZA kinetics in non-small cell lung cancer patients. [2017]