Safety of N-13 Ammonia PET MPI

Overseen By Daniel Juneau, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Disqualifiers: Pregnancy, Claustrophobia, Breastfeeding, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

20000 Participants Needed

Trial Summary

What is the purpose of this trial?

Positron emission tomography (PET) myocardial perfusion imaging (MPI) is an examination that helps to assess the function and perfusion of the heart. Completion of this examination requires the injection of a small dose of a radiotracer (a radioactive substance). PET MPI is a state-of-the-art non-invasive cardiac imaging tool. The main goal of the PET MPI examination is to assess if one or more of the arteries feeding blood to your heart are blocked. This examination replaces an older technology (single photon emission computed tomography, or SPECT), and allows the obtention of more accurate information, and new information that the older SPECT technology did not assess. The radiation dose received as part of the procedure is also smaller with PET versus SPECT. One of the substances which can be used for PET MPI is called N-13 ammoniac (NH3). For this clinical study, NH3 which will be produced at the Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), per the standards and methods prescribed by Health Canada. NH3 is not currently approved for clinical use by Health Canada. It is thus considered and experimental substance in the context of this study. Participants will undergo PET MPI with the CRCHUM NH3. The PET MPI procedure itself is not an experimental procedure and is not part of the research protocol. Only the use of NH3 produced at the CRCHUM is experimental. The main objective of this research study is to validate the production process and assess the safety of the NH3 produced at the CRCHUM cyclotron. Secondary objectives include the assessment of prescription practices amongst physicians who refer patients for PET MPI, and how they will change over time.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a contraindication (a specific reason not to use) to certain stress test medications like dipyridamole, aminophylline, or dobutamine, you may not be eligible to participate.

How is the drug N-13 ammonia different from other treatments for myocardial perfusion imaging?

N-13 ammonia is unique because it is a radiotracer used in PET scans to assess blood flow in the heart, offering high-quality imaging. Unlike other treatments, it requires a specialized production system due to its short half-life and complexity, which limits its widespread use despite its favorable properties. ^{1 2 3 4 5}

Research Team

Daniel Juneau, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

This trial is for adults needing a PET myocardial perfusion imaging test at the Centre hospitalier de l'Université de Montréal. It's not for pregnant or breastfeeding women (unless they stop breastfeeding), people who are claustrophobic, or those with contraindications to certain cardiovascular stress tests.

Inclusion Criteria

Adult patient being referred for clinically indicated positron emission tomography myocardial perfusion imaging at the Centre hospitalier de l'Université de Montréal

Exclusion Criteria

Claustrophobic patient unable to undergo the examination

I am breastfeeding and not willing to stop.

I cannot take certain heart stress test drugs or do an exercise stress test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive N-13 ammonia intravenous injection for PET MPI

1 day

1 visit (in-person)

Follow-up

Participants are monitored for adverse reactions to the N-13 ammonia injection

1 hour

1 visit (in-person)

Treatment Details

Interventions

• N-13 ammonia intravenous injection

Trial Overview The study is testing the safety of N-13 ammonia produced by CRCHUM as a radiotracer in PET scans for heart function and blood flow. The focus is on validating the production process and assessing any changes in physician prescription practices over time.

Participant Groups

Group I: Main arm Experimental Treatment 1 Intervention

N-13 ammonia intravenous injection; 2 injections, 3-7 MBq/kg per injection

N-13 ammonia intravenous injection is already approved in United States, European Union for the following indications:

Approved in United States as Ammonia N 13 Injection for:

• Diagnostic PET imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease.

Approved in European Union as N-13 Ammonia for:

• Diagnostic PET imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease.

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Findings from Research

The production process for the PET radiopharmaceutical [N]NH3 was validated to ensure high safety and purity, achieving a radiochemical yield of 26.3% to 61.5% and 100% radiochemical purity, with no bacterial growth detected in sterility tests.

The careful standardization of all production steps, including online purification and additional contaminant analysis, ensures that [N]NH3 is safe for human use in PET imaging of the myocardium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The strange case of the [13N]NH3: validation of the production process for human use. Statuto, M., Galli, E., Bertagna, F., et al.[2019]

N13-ammonia PET imaging using the Ionetix ION-12SC system produced high-quality myocardial perfusion images in 97 patients, with 91.8% of images rated as good or excellent, indicating its efficacy for clinical use.

The radiation exposure for patients was relatively low, with doses of 0.7 mSv for rest scans and 2.1 mSv for rest-stress scans, suggesting that N13-ammonia PET imaging is a safe option for assessing heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial clinical experience of N13-ammonia myocardial perfusion PET/CT using a compact superconducting production system. Pieper, J., Patel, VN., Escolero, S., et al.[2023]

The study successfully produced [13N]ammonia in high yields (up to 800 mCi) using a novel in-line processing method with irradiated water, demonstrating an efficient approach for generating this radiopharmaceutical for PET imaging.

Combining hydrogen and ethanol as target additives improved the production efficiency of [13N]ammonia at high beam doses, suggesting a potential optimization strategy for radiopharmaceutical synthesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-target production of [13N]ammonia: target design, products, and operating parameters. Berridge, MS., Landmeier, BJ.[2019]

In a study involving nine healthy volunteers, over 90% of the blood activity from [13N] ammonia was identified as the tracer within the first two minutes post-injection, indicating its rapid uptake.

However, by 3-5 minutes, significant contamination from metabolites like [13N]glutamine and urea emerged, accounting for 18%-50% of blood activity, highlighting the need for corrections in arterial input function to ensure accurate myocardial blood flow quantification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic fate of [13N]ammonia in human and canine blood. Rosenspire, KC., Schwaiger, M., Mangner, TJ., et al.[2015]

The biodistribution study of (13)N-ammonia in five healthy subjects showed that the highest concentrations were found in the heart and liver, indicating these organs are key areas for this tracer's action.

The effective dose of radiation from (13)N-ammonia was found to be relatively low (6.58E-03 mSv/MBq), suggesting that it is safe for use in multiple PET scans per year without significant radiation risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution and estimation of radiation-absorbed doses in humans for 13N-ammonia PET. Yi, C., Yu, D., Shi, X., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

The strange case of the [13N]NH3: validation of the production process for human use. [2019]

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

Initial clinical experience of N13-ammonia myocardial perfusion PET/CT using a compact superconducting production system. [2023]

3. England pubmed.ncbi.nlm.nih.gov

In-target production of [13N]ammonia: target design, products, and operating parameters. [2019]

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

Metabolic fate of [13N]ammonia in human and canine blood. [2015]

5. Japan pubmed.ncbi.nlm.nih.gov

Biodistribution and estimation of radiation-absorbed doses in humans for 13N-ammonia PET. [2015]