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

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

Compensation: Varies

Number of Visits: 2

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Peripheral artery disease is a worldwide problem, leading to high mortality and mobility. Critical limb ischemia (CLI) is associated with high risk of amputation with the subsequent decreased in life quality. Endovascular therapy is now considered the primary treatment option in these patients to improve the vascularity and prevent amputations. In recent years, development of molecular imaging tools are now become available. A recent radio tracer named 18F-Fluoroazomycin Arabinoside (FAZA) its an specific marker of hypoxia in the tissues and has been used in multiples studies. This tracer can be used in PET/MR scan providing a potentially power diagnostic tool in patients with CLI, allowing in one diagnostic study the evaluation of location and degree of hypoxia in the extremity tissues. This diagnostic tool may offer a better assessment pre and post standard of care endovascular treatment for the patients. Moreover, some of the patients treated with endovascular therapy may not have a favorable outcome, without a clear reason explaining this situation. We will try to find some predictor model in the FAZA PET/MR that can explain the different outcomes and may help clinicians choose the best treatment option in specific cases. Thirdly, post processing for optimization of the MR sequences in patients with CLI will be performed at the MR component of the PET. There would thus be great clinical interest in developing non-invasive tools that could provide more accurate diagnostic information compared to traditional tests for these patients population.

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 data supports the effectiveness of the drug 18F-Fluoroazomycin Arabinoside (FAZA) for Critical Limb Ischemia?

The research primarily discusses the use of FAZA as a PET imaging agent for detecting low oxygen levels in tumors, which is not directly related to treating Critical Limb Ischemia. However, its ability to highlight areas with low oxygen might indirectly suggest potential in identifying ischemic regions, although this is not directly proven for this condition. ^{1 2 3 4 5}

How does the FAZA PET/MRI treatment for critical limb ischemia differ from other treatments?

FAZA PET/MRI is unique because it uses a PET tracer called FAZA to identify areas of low oxygen (hypoxia) in tissues, which is not a standard approach for treating critical limb ischemia. This method is typically used in cancer to detect tumor hypoxia, making its application in limb ischemia novel. ^{1 2 3 5 6}

Research Team

Patrick Veit-Haibach, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

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

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

References

1. 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]

2. 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]

3. 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]

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

Imaging hypoxia in xenografted and murine tumors with 18F-fluoroazomycin arabinoside: a comparative study involving microPET, autoradiography, PO2-polarography, and fluorescence microscopy. [2017]

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

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

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

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