Myocardial Perfusion Imaging for Coronary Artery Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Washington University School of Medicine
Must not be taking: Chemotherapeutic agents
Disqualifiers: Heart failure, Cardiomyopathy, Pregnancy, others
No Placebo Group
Trial Summary
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.
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.
12345What 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.
12345Is 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.
12678Eligibility 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 am between 18 and 99 years old.
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.
+10 more
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: Symptomatic Patients with Normal Clinical SPECT or PETExperimental Treatment1 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 PETExperimental Treatment1 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 Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington University School of MedicineSaint Louis, MO
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
National Institutes of Health (NIH)Collaborator
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Noninvasive evaluation of regional myocardial perfusion in 112 patients using a mobile scintillation camera and intravenous nitrogen-13 labeled ammonia. [2019]The short half-life positron emitter 13N, as labeled ammonia (13NH4+), was evaluated as a myocardial imaging agent. Regional myocardial uptake of 13NH4 correlated with the distribution of labeled microspheres in experimental myocardial infarction. Using intravenous 13NH4+, myocardial scintigraphy was performed in 85 cardiac patients and 27 normal subjects. Ninety-five scintigrams were suitable for analysis. Eighteen of 24 normal subjects had homogeneous myocardial images; six had inhomogeneous images attributable to early technical problems. Perfusion defects were observed in the scintigrams of 82% (57/65) of patients with coronary artery disease, being most common in patients with myocardial infarction (27/28). Six sequential studies showed changes in perfusion consistent with the clinical course of each patient. Scintigraphic abnormalities were also observed in 4/6 patients with valvular heart disease. 13NH4+ myocardial scintigraphy is a valid and sensitive method of assessing regional myocardial perfusion and is especially useful for sequential imaging at short intervals.
Nitrogen-13-labeled ammonia for myocardial imaging. [2019]Cyclotron-produced nitrogen-13 (half-life 10 min), as labeled ammonia (13NH4+), has been evaluated as a myocardial perfusion imaging agent. The regional myocardial uptake of 13NH4+ has been shown to be proportional to regional tissue perfusion in animal studies. Intravenously administered 13NH4+ is rapidly cleared from the circulation, being extracted by the liver (15%), lungs, myocardium (2%-4%), brain, kidney, and bladder. Myocardial ammonia is metabolized mainly to glutamine via the glutamine synthetase pathway. Pulmonary uptake is substantial, but usually transient, except in smokers where clearance may be delayed. The position annihilation irradiation (511 keV) of 13N may be imaged with a scintillation camera, using either a specially designed tungsten collimator or a pinhole collimator. After early technical problems with collimation and the production method of 13NH4+ were overcome, reproducible high quality myocardial images were consistently obtained. The normal myocardial image was established to be of a homogeneous "doughnut" configuration. Imaging studies performed in patients with varying manifestations of ischemic and valvular heart disease showed a high incidence of localized perfusion defects, especially in patients with acute myocardial infarction. Sequential studies at short intervals in patients with acute infarction showed correlation between alterations in regional perfusion and the clinical course of the patient. It is concluded that myocardial imaging with 13NH4+ and a scintillation camera provides a valid and noninvasive means of assessing regional myocardial perfusion. This method is especially suitable for sequential studies of acute cardiac patients at short intervals. Coincidence imaging of the 511 keV annihilation irradiation provides a tomographic and potentially quantitative assessment of the regional myocardial uptake of 13NH4+.
68Ga[Ga]-Galmydar: Biodistribution and radiation dosimetry studies in rodents. [2021]Label="INTRODUCTION"> 68Ga[Ga]-Galmydar is an avid transport substrate of ABCB1 (P-Glycoprotein; 170kDa plasma membrane protein), breast cancer resistance protein (BCRP; ABCG2; 72kDa), penetrates human epidermal carcinoma (KB3-1), breast cancer (MCF7), embryonic kidney (HEK 293) tumor cells and rat cardiomyoblasts, and localizes within the mitochondria of tumor and myocardium cells. 68Ga[Ga]-Galmydar excretes from blood pool quickly, and shows stable retention within rat myocardium in vivo for extended periods, therefore, the agent shows potential to enable myocardial perfusion imaging. The PET tracer also demonstrates ability to probe viability of the blood brain barrier (BBB) in WT mice compared with their mdr1a/1b(-/-) (dKO) and mdr1a/1b/ABCG2(-/-/-) (t-KO) counterparts. Herein, we report dosimetry data for 68Ga[Ga]-Galmydar in mice, and extrapolate that information to determine effective dose (ED) for human studies.
Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. [2015]We evaluated four potential gallium-68 (68Ga)-labeled tracers for positron emission tomography (PET) imaging of myocardial perfusion in comparison with oxygen-15-labeled water ([15O]water) in healthy pigs. Four hexadentate salicylaldimine ligands derived from bis(3-aminopropyl)ethylenediamine (BAPEN) that showed promise in previous rat experiments were selected for this study.
Production of [13N]ammonia from [13C]methanol on a 7.5 MeV cyclotron using 13C(p, n)13N reaction: Detection of myocardial infarction in a mouse model. [2020][13N]Ammonia is commonly produced using 16O(p, α)13N reaction but one of the limiting factor of this reaction is the relatively small nuclear cross-section at proton energies of <10 MeV. An alternative production method using 13C(p, n)13N reaction, which has a higher nuclear cross-section at low proton energies, is more suitable for a preclinical PET imaging facility equipped with a <10 MeV cyclotron. Here, we report a novel method to produce [13N]ammonia from [13C]methanol for preclinical use on a 7.5 MeV cyclotron. A tantalum solution target (80 μl) consisting of a havar window supplied by the cyclotron manufacturer for the production of [18F]fluoride was used without any modifications. The final bombardment parameters were optimized as follow: [13C]methanol concentration in target solution - 10%, bombardment time - 8 min, and beam current - 2.2 μA. These parameters provided doses of [13N]ammonia which were sufficient to conduct preclinical PET imaging studies in a mouse model of myocardial infarction. Under optimized conditions, the operational lifetime of the target was approximately 150 μAmin. Radionuclide identity of the product as 13N was confirmed by measuring the decay half-life and its radionuclide purity was confirmed by γ-ray spectroscopic analysis. Gas chromatography revealed that the final [13N]ammonia dose was not distinguishable from water, showing no traces of methanol. As expected, PET/CT imaging in healthy CD-1 mice indicated the accumulation of [13N]ammonia in myocardial tissue; mice with myocardial infarction created by left ascending coronary ligation showed clear perfusion deficit in affected tissue. This work demonstrates the proof-of-concept of using 13C(p, n)13N reaction to produce [13N]ammonia from [13C]methanol with a <10 MeV cyclotron, and its diagnostic application in imaging cardiac perfusion.
[Myocardial positron computed tomography using N-13 ammonia for evaluating coronary artery disease: comparison with thallium-201 emission computed tomography]. [2016]To assess myocardial perfusion in patients with coronary artery disease (CAD), N-13 ammonia positron computed tomography (PCT) was performed for 32 cases, and the PCT images were compared with those of single-photon emission computed tomography (SPECT) using thallium-201. Myocardial perfusion images were obtained with a whole-body multislice PCT device following the intravenous injection of 10 to 20 mCi N-13 ammonia at rest (32 cases) and during exercise (23 cases). Eleven cases underwent serial 15-20 second dynamic studies immediately following the N-13 ammonia injection. Serial dynamic study showed the blood-pool images in the first scan, and enabled assessment of tracer washout from the blood-pool, and the lung as well as washin into the myocardium. PCT provided clear resting myocardial perfusion images in all cases. PCT images were of higher quality than those of SPECT due to higher spatial resolution with less statistical noise, allowing delineation of the right ventricular myocardium and papillary muscles in many cases. Both PCT and SPECT detected perfusion abnormalities in 18 of the 19 cases with myocardial infarction, without false positive findings. PCT yielded stress myocardial images and permitted comparative evaluations of myocardial perfusions at rest and during exercise in all 23 cases. Perfusion abnormalities were detected in 14 cases (74%) at rest and in 18 cases (95%) during exercise among 19 patients with CAD. No false positives were observed, either by resting or stress PCT imaging. Stress myocardial PCT identified regional perfusion abnormalities in 30 of the 34 regions supplied by stenosed vessels (88%). High resolution PCT images enabled precise evaluation of myocardial perfusions which proved valuable for assessing myocardial perfusions before and after aorto-coronary bypass surgery. The present study proved advantages of N-13 ammonia PCT in creating three-dimensional high resolution images of the myocardium, which facilitates precise evaluation of myocardial perfusions. Furthermore, its potential capabilities in quantifying coronary reserve function will be very useful. This method should provide valuable pathophysiological information for CAD, as well as for metabolic PCT imaging.
Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography. [2019]In order to evaluate the detectability of coronary artery disease (CAD) with positron-emission computed tomography (PET), we performed 13N-ammonia myocardial PET scanning at rest and with exercise loading in 20 normal subjects and 40 patients with CAD, by means of a high-resolution, multi-slice, whole-body PET scanner. Myocardial PET scanning was performed 3 minutes after injection of 13N-ammonia at rest and during exercise. The circumferential profile analysis of resting PET images revealed regional hypoperfusion in 96% of CAD patients with previous myocardial infarction and in 29% of those without infarction. Exercise PET studies showed high sensitivity (93%) in detecting CAD without myocardial infarction, whereas no abnormal hypoperfusion was detected in normal subjects. Segmental analysis of regional myocardial perfusion with exercise stress identified 67 of 75 stenosed vessels (89%). We conclude that 13N-ammonia myocardial PET with exercise loading provides high-quality tomographic images of regional myocardial perfusion and is a valuable technique for detecting CAD.
Myocardial positron computed tomography with 13N-ammonia at rest and during exercise. [2019]To assess the value of myocardial-perfusion positron computed tomography (PCT) for the evaluation of coronary artery disease (CAD), 13N-ammonia PCT using a whole-body multislice PCT device was performed at rest and during exercise in 6 normal subjects and 19 patients with angiographically documented CAD. The 13N-ammonia distribution in the myocardium was assessed both qualitatively and quantitatively. At rest and during exercise, the tracer distribution was homogeneous in the 6 normal cases. In the 19 patients with CAD, regional hypoperfusion was observed in 14 cases (74%) at rest and in 18 cases (95%) during exercise. Additional perfusion abnormalities were detecting during exercise in 12 cases. Segmental analysis of the myocardial perfusion identified 30 out of 34 stenosed vessels (88%) during exercise, with only one false-positive finding of diseased vessels (specificity, 98%). For the quantitative analysis of myocardial perfusion by PCT, the percentage of change in the tracer concentration in the same region between the rest and stress images was calculated. The concentration was slightly increased in normal myocardial segments (14.4% +/- 5.8%; P less than 0.001), whereas in CAD, it was significantly decreased in segments with stenosed vessels (-18.0% +/- 18.3%; P less than 0.02). We conclude that 13N-ammonia PCT at rest and during exercise provides high-quality images, and is a sensitive and effective technique for detecting CAD and identifying individual stenosed vessels. Furthermore, this technique makes possible quantitative assessment of the coronary reserve function.