Myocardial Perfusion Imaging for Coronary Artery Disease

Overseen By Kitty D Harrison, R.N

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington University School of Medicine

Must not be taking: Chemotherapy agents

Disqualifiers: Heart failure, Cardiomyopathy, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

Do I need to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking chemotherapeutic agents, you must not have received them within 6 months of enrollment. It's best to discuss your specific medications with the trial team.

What data supports the idea that Myocardial Perfusion Imaging for Coronary Artery Disease is an effective treatment?

The available research shows that Myocardial Perfusion Imaging using 13N-ammonia is effective in identifying blood flow issues in the heart. In one study, 82% of patients with coronary artery disease showed blood flow problems, especially those who had heart attacks. This imaging method is also useful for tracking changes in heart blood flow over time, which can help doctors understand how a patient's condition is progressing. Another study confirmed that this imaging technique provides clear and reliable images of the heart, making it a valuable tool for assessing heart health. ^{1 2 3 4 5}

What safety data is available for myocardial perfusion imaging using 13N-ammonia and 68Ga-Galmydar?

The safety data for myocardial perfusion imaging using 13N-ammonia and 68Ga-Galmydar includes several studies. For 13N-ammonia, it has been evaluated as a myocardial imaging agent, showing rapid clearance from circulation and proportional uptake to regional tissue perfusion. It has been used in both animal and human studies, demonstrating its validity and sensitivity in assessing regional myocardial perfusion, especially useful for sequential imaging at short intervals. For 68Ga-Galmydar, biodistribution and radiation dosimetry studies in rodents have been conducted, showing quick excretion from the blood pool and stable retention in the myocardium, indicating potential for myocardial perfusion imaging. These studies provide foundational safety data for the use of these agents in myocardial perfusion imaging. ^{1 2 3 4 5}

Is the drug 13N-ammonia a promising treatment for coronary artery disease?

Yes, 13N-ammonia is a promising drug for coronary artery disease. It helps create clear and detailed images of the heart, which can show how well blood is flowing. This is especially useful for detecting problems in the heart's blood supply, both at rest and during exercise. It can also help doctors track changes in heart health over time. ^{1 2 6 7 8}

What is the purpose of this trial?

A single center, phase 0/1 clinical imaging study designed to assess the role of \[68Ga\]Galmydar PET/CT imaging in human subjects.

Research Team

Pamela K Woodard, M.D

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for men and women aged 18-99 with a history of heart issues, specifically those who've had certain types of heart scans showing possible blockages and are referred for further testing. It's not suitable for pregnant or breastfeeding women, individuals over 500 lbs, those with severe claustrophobia, uncontrolled high blood pressure, recent major heart procedures, chemotherapy within the last six months, serious lung diseases with wheezing, severe heart failure or conditions that prevent stress testing.

Inclusion Criteria

I've had a heart scan showing reduced blood flow or a normal heart scan.

Exclusion Criteria

I have a type of heart disease not caused by blocked arteries.

Your blood pressure is too low at the start of the trial (systolic blood pressure less than 90 mmHg, diastolic blood pressure less than 50 mmHg).

I am unable to understand or sign the consent form.

Treatment Details

Interventions

• 13N-ammonia
• Ga-68 Galmydar

Trial Overview The study is evaluating [68Ga]Galmydar PET/CT imaging to see how well it can identify areas of the heart muscle that aren't getting enough blood flow in patients suspected to have coronary artery disease. This phase 0/1 trial will compare Galmydar images against traditional SPECT MPI results.

Participant Groups

Group I: Symptomatic Patients with Normal Clinical SPECT or PET Experimental Treatment 1 Intervention

Patients in this group have had a clinical SPECT or PET MPI examination that is normal and do not have an invasive coronary angiography (ICA) referral. Participants will receive one \[68Ga\]Galmydar intravenous administration, 2 mCi during rest for the \[68Ga\]Galmydar PET MPI.

Group II: Symptomatic Patients with Abnormal Clinical SPECT or PET Experimental Treatment 1 Intervention

Patients in this group have had a clinical SPECT or PET MPI examination that is positive for ischemia in two myocardial segments and have been referred for invasive coronary angiography (ICA) as part of their routine standard-of-care. Subjects will undergo \[68Ga\]Galmydar PET/CT prior to any intervention. Participants will receive one \[68Ga\]Galmydar intravenous administration, 2 mCi during rest.

Group III: Asymptomatic Subjects (Normal Controls) Experimental Treatment 2 Interventions

Normal control subjects are asymptomatic, without history of cardiovascular disease or significant cardiovascular risk factors. These participants will receive two \[68Ga\]Galmydar intravenous administrations, 2 mCi during rest and 4 mCi during stress for the \[68Ga\]Galmydar PET MPI performed on Imaging Day-1. On Imaging Day-2, asymptomatic subjects will receive two single intravenous administrations each of 10 mCi of \[13N\]Ammonia during the rest and stress PET MPI. \[68Ga\]Galmydar and \[13N\]Ammonia imaging visits will be separated by a minimum of 3 days.

13N-ammonia is already approved in United States for the following indications:

Approved in United States as Ammonia N 13 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?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

The use of 13N-labeled ammonia (13NH4+) for myocardial imaging has been shown to correlate well with actual blood flow in heart tissue, making it a reliable method for assessing heart health.

In a study involving 85 cardiac patients, 13NH4+ scintigraphy detected perfusion defects in 82% of patients with coronary artery disease, demonstrating its effectiveness in identifying heart issues, particularly in those with myocardial infarction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive evaluation of regional myocardial perfusion in 112 patients using a mobile scintillation camera and intravenous nitrogen-13 labeled ammonia. Walsh, WF., Harper, PV., Resnekov, L., et al.[2019]

Cyclotron-produced nitrogen-13 labeled ammonia (13NH4+) is an effective and noninvasive agent for myocardial perfusion imaging, showing a strong correlation between regional uptake and tissue perfusion in patients with heart conditions.

This imaging technique allows for high-quality, reproducible myocardial images and is particularly useful for monitoring changes in regional perfusion in acute cardiac patients over short intervals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrogen-13-labeled ammonia for myocardial imaging. Walsh, WF., Fill, HR., Harper, PV.[2019]

68Ga[Ga]-Galmydar shows potential as a PET imaging probe for myocardial perfusion, demonstrating stable retention in rat myocardium and quick excretion from the blood, indicating its efficacy for imaging applications.

Radiation dosimetry studies in mice suggest that 68Ga[Ga]-Galmydar has a low effective dose (0.021 mGy/MBq for males and 0.023 mGy/MBq for females), with the kidneys receiving the highest dose, making it a safe candidate for further human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga[Ga]-Galmydar: Biodistribution and radiation dosimetry studies in rodents. Sivapackiam, J., Laforest, R., Sharma, V.[2021]

In a study involving 14 healthy pigs, four gallium-68 (68Ga)-labeled tracers were evaluated for their effectiveness in PET imaging of myocardial perfusion, but all showed slow accumulation in the heart over time.

The best-performing tracer, [68Ga][Ga-(sal)2BAPDMEN]1+, had the highest myocardial uptake, yet there was no correlation between its uptake and actual myocardial perfusion measured with [15O]water, indicating these tracers are not suitable for clinical use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. Tarkia, M., Saraste, A., Saanijoki, T., et al.[2015]

A novel method for producing [13N]ammonia from [13C]methanol using the 13C(p, n)13N reaction on a <10 MeV cyclotron was successfully developed, providing sufficient doses for preclinical PET imaging studies.

The produced [13N]ammonia showed no traces of methanol and effectively demonstrated cardiac perfusion imaging in mouse models, indicating its potential for diagnosing myocardial infarction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production of [13N]ammonia from [13C]methanol on a 7.5&#8239;MeV cyclotron using 13C(p, n)13N reaction: Detection of myocardial infarction in a mouse model. Nkepang, GN., Gali, H., Houson, H., et al.[2020]

N-13 ammonia positron computed tomography (PCT) provided high-resolution myocardial perfusion images that were clearer and of better quality than those obtained from single-photon emission computed tomography (SPECT), allowing for detailed assessment of heart structures and perfusion.

In patients with coronary artery disease (CAD), PCT effectively detected perfusion abnormalities during both rest and exercise, identifying issues in 74% of cases at rest and 95% during exercise, without any false positives, making it a reliable tool for evaluating heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Myocardial positron computed tomography using N-13 ammonia for evaluating coronary artery disease: comparison with thallium-201 emission computed tomography]. Tamaki, N., Yonekura, Y., Kodama, S., et al.[2016]

In a study involving 60 participants (20 normal subjects and 40 patients with coronary artery disease), 13N-ammonia myocardial PET scanning demonstrated high sensitivity (93%) for detecting coronary artery disease during exercise, especially in patients without prior myocardial infarction.

The technique effectively identified regional hypoperfusion in 96% of CAD patients with a history of myocardial infarction and successfully detected 89% of stenosed vessels, highlighting its efficacy in diagnosing coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography. Yonekura, Y., Tamaki, N., Senda, M., et al.[2019]

Myocardial-perfusion positron computed tomography (PCT) using 13N-ammonia is highly effective in detecting coronary artery disease (CAD), identifying 88% of stenosed vessels during exercise in a study of 25 subjects (6 normal and 19 with CAD).

The technique not only provides high-quality imaging but also allows for quantitative assessment of coronary reserve function, showing significant decreases in tracer concentration in CAD patients compared to normal segments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial positron computed tomography with 13N-ammonia at rest and during exercise. Tamaki, N., Yonekura, Y., Senda, M., et al.[2019]

References

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

Noninvasive evaluation of regional myocardial perfusion in 112 patients using a mobile scintillation camera and intravenous nitrogen-13 labeled ammonia. [2019]

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

Nitrogen-13-labeled ammonia for myocardial imaging. [2019]

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

68Ga[Ga]-Galmydar: Biodistribution and radiation dosimetry studies in rodents. [2021]

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

Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Production of [13N]ammonia from [13C]methanol on a 7.5&#8239;MeV cyclotron using 13C(p, n)13N reaction: Detection of myocardial infarction in a mouse model. [2020]

6. Japan pubmed.ncbi.nlm.nih.gov

[Myocardial positron computed tomography using N-13 ammonia for evaluating coronary artery disease: comparison with thallium-201 emission computed tomography]. [2016]

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

Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Myocardial positron computed tomography with 13N-ammonia at rest and during exercise. [2019]