FAZA PET/MRI for Critical Limb Ischemia

Overseen By Patrick Veit-Haibach, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Pregnancy, Metallic hardware, others

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

Compensation: Varies

Number of Visits: 2

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve how doctors diagnose and treat critical limb ischemia (CLI), a condition that can lead to amputations and reduce quality of life. The study uses a special imaging scan called FAZA PET/MRI, which involves 18F-Fluoroazomycin Arabinoside (FAZA), to identify areas of low blood flow in the legs. This scan might help doctors select the best treatment plans for patients. Individuals with CLI who are considering surgery to improve leg blood flow might be suitable candidates for this trial. As an unphased trial, this study offers patients the chance to contribute to innovative research that could enhance future diagnostic and treatment options for CLI.

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.

What prior data suggests that the FAZA PET/MRI scan is safe for patients with critical limb ischemia?

Research has shown that 18F-Fluoroazomycin Arabinoside (FAZA) is being studied as a special dye for PET scans to identify areas in the body with low oxygen. Studies have found FAZA useful for detecting low oxygen levels, known as hypoxia, in tissues. This can help doctors understand issues in areas with poor blood flow, such as in critical limb ischemia.

Although limited safety data exists specifically for critical limb ischemia, FAZA has been safely used in other studies for cancer imaging. No major safety problems were reported in those cases, suggesting it is generally well-tolerated.

Since this study focuses on imaging rather than treating a condition, the risks are usually lower than those involving drugs or surgeries. However, discussing any concerns with a healthcare provider is always advisable if considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using 18F-Fluoroazomycin Arabinoside (FAZA) for critical limb ischemia because it offers a new way to visualize tissue oxygenation levels through PET/MRI scans. Unlike traditional treatments that primarily focus on improving blood flow or managing symptoms, FAZA highlights areas of low oxygen in tissues, which can help doctors tailor treatments more precisely. This imaging technique could lead to more personalized and effective strategies for managing and treating critical limb ischemia, potentially improving patient outcomes.

What evidence suggests that the FAZA PET/MRI scan is effective for diagnosing critical limb ischemia?

Research has shown that 18F-Fluoroazomycin Arabinoside (FAZA) is used in PET/MRI scans to detect low oxygen levels in tissues, which is crucial in conditions like critical limb ischemia (CLI). Studies have demonstrated that FAZA helps doctors visualize and quantify low oxygen in areas affected by CLI. This information is valuable for understanding why some patients do not respond well to treatments like endovascular therapy. By identifying specific areas with low oxygen, FAZA PET/MRI may assist doctors in creating better treatment plans to improve outcomes for those with CLI. Although FAZA is not a treatment, it plays a promising role in enhancing diagnosis and treatment planning for this condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Patrick Veit-Haibach, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for adults over 18 with critical limb ischemia (CLI) who are candidates for revascularization treatment to improve blood flow and prevent amputation. Women of childbearing age must have a negative pregnancy test and all participants must consent to the study.

Inclusion Criteria

A negative urine or serum pregnancy test in women of child-bearing age;

Ability to provide written informed consent to participate in the study.

I have severe leg circulation problems and am a candidate for surgery to improve blood flow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Assessment

FAZA PET/MRI scan to evaluate hypoxia in limb tissues before endovascular treatment

2-3 weeks

1 visit (in-person)

Endovascular Treatment

Participants undergo standard of care endovascular therapy to improve vascularity

1 week

Post-Treatment Assessment

FAZA PET/MRI scan to evaluate changes in hypoxia after endovascular treatment

4-6 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-Fluoroazomycin Arabinoside (FAZA)

Trial Overview The trial is testing FAZA PET/MRI scans as a diagnostic tool in CLI patients. It aims to evaluate tissue hypoxia before and after standard endovascular therapy, potentially helping predict outcomes and guide treatment choices.

How Is the Trial Designed?

Group I: FAZA PET/MRI scan Experimental Treatment 1 Intervention

PET/MRI scan using radiotracer 18F-Fluoroazomycin Arabinoside

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12033150/

Measuring hypoxia in chronic limb-threatening ischemia ... In this study, we use dynamic 18 F-FAZA PET-imaging as a method of measuring hypoxia as a marker associated with CLTI, on twelve patients identified with CLTI.

2. jnm.snmjournals.org jnm.snmjournals.org/content/64/supplement_1/P1142

Exploration of 18FAZA-PET kinetic modelling in patient with ... In this study, we assessed the pharmacokinetics of 18F-FAZA in patients with known CLTI.

3. withpower.com withpower.com/trial/phase-ischemia-7-2019-8cb6a

FAZA PET/MRI for Critical Limb Ischemia What data supports the effectiveness of the drug 18F-Fluoroazomycin Arabinoside (FAZA) for Critical Limb Ischemia? The research primarily discusses the use of ...

4. researchgate.net researchgate.net/publication/391204006_Measuring_hypoxia_in_chronic_limb-threatening_ischemia_using_F-FAZA_kinetic_modelling_-_a_pilot_study

Measuring hypoxia in chronic limb-threatening ischemia ... Purpose To evaluate the prognostic value of [¹⁸F]FAZA PET in predicting long-term clinical outcomes of critical limb-threatening ischemia (CLTI) ...

5. mdpi.com mdpi.com/2379-139X/10/9/102

18F-Fluoroazomycin Arabinoside (FAZA) PET/MR as a ... Demographic data, including clinical and surgical stage, pathology regression grade, and clinical outcome data, are depicted in Table 1. In ...

6. withpower.com withpower.com/trial/phase-1-breast-neoplasms-8-2017-f1484

18F-AZA PET-CT Imaging for Cancer Diagnosis Is 18F-AZA PET-CT Imaging safe for humans? The studies on 18F-fluoroazomycin arabinoside (FAZA) primarily focus on its use as a PET tracer for identifying tumor ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12394084/

A Phase 1/2a Clinical Trial to Evaluate the Efficacy and ... Critical limb ischemia (CLI) is a severe manifestation of peripheral arterial disease, often resulting in ischemic rest pain, non-healing ulcers, or gangrene.

8. ejnmmires.springeropen.com ejnmmires.springeropen.com/articles/10.1186/s13550-025-01243-5

Measuring hypoxia in chronic limb-threatening ischemia using ... In this study, we use dynamic 18 F-FAZA PET-imaging as a method of measuring hypoxia as a marker associated with CLTI, on twelve patients identified with CLTI.