Cardiac PET
Exploring cardiological indications in PET and PET/CT
According to the Center for Disease Control (CDC), cardiovascular disease (CVD) remains the leading cause of death and disease burden worldwide, accounting for 874,613 deaths in the United States in 2019. CVD includes coronary artery disease (CAD) and stroke. CAD is the most common type of CVD, with more than 18.2 million adults over the age of 20 living with CAD, resulting in 360,900 deaths in 20191. Stroke accounted for 1 in 6 deaths from CVD and more than 795,000 people in the United States suffer a stroke annually.2
Overview
Molecular imaging can aid in the identification of patients with CVD and the stratification of risk for disease. Both PET and SPECT are used for cardiac imaging, with myocardial perfusion imaging (MPI) used most frequently for diagnostic and prognostic information. PET cardiac imaging has been performed for over three decades, but the short half-life and accessibility of high-energy radiopharmaceuticals has inhibited wide adoption.
Currently, there are three FDA-approved radiopharmaceuticals indicated for PET cardiac imaging:
Viability
Myocardial viability imaging
18F FDG PET relies on the metabolic and perfusion properties of the myocardium to identify whether tissue is viable or not, assisting clinicians in determining the appropriate medical and surgical pathways for those suffering from ischemic heart disease (IHD), also known as coronary artery disease (CAD).3
Ischemic heart disease (IHD) affects approximately 126 million people worldwide.4 The aging population and the increasing prevalence of diabetes, obesity, and metabolic syndrome contribute to those suffering from IHD.5 18F FDG PET for cardiac viability has been recognized as a valuable tool for differentiating viable from non-viable myocardial tissue. Identifying patients with partial loss of heart muscle movement or hibernating myocardium is essential in determining compromised ventricular function and appropriateness for revascularization.6 As numbers of those suffering from CAD continue to rise, the use of 18F FDG PET for viability imaging may become more important as a non-invasive exam with superb sensitivity in detecting hibernating viable myocardium and predicting left ventricular functional recovery post-coronary revascularization.7
18F FDG PET differentiates between hibernating-but-viable myocardium from infarcted myocardium, which is not visualized at rest and does not improve post-revascularization. Hibernating myocardium is referred to as severely hypo-perfused myocardium with resting wall motion abnormalities but with preserved viability. It appears as a severe resting perfusion defect on MPI but displays glucose metabolism and normal 18F FDG uptake on PET.8
Data courtesy of Manchester Royal Infirmary, Manchester, United Kingdom
Perfusion-viability mismatch with low resting perfusion and normal
18F FDG uptake on PET/CT is a hallmark of viable but severely ischemic myocardium and guides decision making for revascularization such as coronary stenting or bypass grafting.7
PPV = positive predictive value
NPV = negative predictive value
18F FDG PET and other non-invasive modalities for identifying myocardial viability
18F FDG sensitivity
18F FDG uptake in the myocardium occurs when it competes with glucose for transportation into the sarcolemma for hexokinase-mediated phosphorylation.11
For optimal myocardium uptake with 18F FDG, the patient should be adequately prepared before the 18F FDG injection by shifting the heart's metabolism to maximize glucose uptake and, ultimately, the uptake of 18F FDG.12 The SNMMI and ASNC offer protocols to achieve proper patient preparation for glucose loading.
18F FDG PET imaging is CMS-approved for patients with coronary artery disease and left ventricular dysfunction, and when used together with myocardial perfusion imaging to identify left ventricular myocardium with residual glucose metabolism and possible reversible loss of systolic function.13
Myocardial perfusion imaging (MPI)
Myocardial perfusion imaging (MPI) is a necessary and essential tool to assess myocardial blood supply. There are several methods for performing MPI including SPECT MPI, cardiac MRI perfusion, myocardial contrast echo, cardiac computed tomography (CT), and PET MPI.14 MPI exams are often ordered for perioperative cardiovascular evaluation and chest pain. MPI is used to evaluate and detect ischemic heart disease (IHD) and to assess left-ventricular function and myocardial viability.15
MPI has been used by physicians since the 1980s and is now the most-performed nuclear cardiology exam done annually. SPECT MPI is highly utilized due to the ease of access to low-energy radiopharmaceuticals. However, the broader use of PET MPI has emerged more recently due to its superior characteristics compared to other non-invasive exams.16
In 2016, two of the leading industry organizations – the American Society of Nuclear Cardiology (ASNC) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) made a joint statement that there is a significant underutilization of PET MPI in spite of the advantages it offers in assessing suspected or known CAD. It was also noted that PET MPI is the preferred test for all patients recommended for pharmacologic stress testing. The joint statement strongly recommended PET MPI for patients with a previous inconclusive exam, body habitus restrictions, high-risk patients, patients that require reduced radiation exposure, and when determining myocardial blood flow (MBF), asserting the benefit to clinicians when determining a patient's care pathway.17
Data courtesy of Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Scan acquisition
1 bed position/7 minutes per bed
Image reconstruction
128 x 128 matrix, OSEM3D+TOF 4i10s
Gaussian filter 10
Injected dose
Rubidium chloride (82Rb) Injection
Rest: 20 mCi (740 MBq)
Stress: 20 mCi (740 MBq) CT
Scan parameters
80 kV/45 ref mAs
High-energy PET radiopharmaceuticals for MPI have several advantages over low-energy SPECT tracers including:18
- Higher spatial and contrast resolution
- Improved count sensitivity
- Improved temporal resolution
- Lower radiation dose
- Shorter acquisition times
Although PET is being used more frequently for cardiac imaging, limitations still impact the widespread utilization of this diagnostic tool.
FDA-approved radiopharmaceuticals for PET MP
Currently there are two FDA-approved radiopharmaceuticals for PET MPI for rest and pharmacologically induced vasodilation stress. Both tracers differ in myocardial uptake, myocardial extraction fraction, positron range, half-life, production, and use in the clinical setting.19
Data courtesy of WVU Medical Center, Morgantown, WV, USA
Scan acquisition
200 x 200 matrix, 3D-OSEM 4i24s
Scan time
7 minutes scan each for rest and stress images
Injected dose
13NH3 20 mCi (740 MBq) rest
13NH3 20 mCi (740 MBq) stress
CT Scan parameters
100 kV / 40 ref mAs
Ammonia N 13 has a short half-life of 9.96 minutes and is cyclotron-produced. Due to the short half-life, tracer availability is limited to imaging centers with a cyclotron on-site or within close proximity. Ammonia N 13 has a positron range of 2.53mm, resulting in intermediate-high image resolution. When injected, it clears rapidly from circulation with only 0.4% remaining after 3.3 minutes and diffuses across the myocardial cell capillary membrane where it is converted to glutamine N 13 by glutamine synthetase, which remains trapped within the tissue.20 The myocardial uptake is proportional to the coronary blood flow. Although ammonia N 13 has a short half-life, it possesses a long biological residence time within the myocardium.19 PET allows for excellent quality MPI and dynamic first-pass imaging with quantification of absolute myocardial blood flow (MBF).20
The use of ammonia N 13 requires an on-site or a nearby cyclotron, slowing adoption of this radiopharmaceutical. See how ammonia N 13 compares to rubidium R 82:
Recent advances in nuclear technology have allowed for the development of a mini-cyclotron system that can be housed within an imaging facility. This new technology may offer imaging centers that did not have access to ammonia N 13 the opportunity to consider offering cardiac PET with this under-utilized radiopharmaceutical.
Data courtesy of Christiana Care Health Systems, Newark, Delaware, USA
Scan acquisition
1 bed position/7 minutes per bed
Ejection fraction (EF): 61%
Image reconstruction
128 x 128 matrix, OSEM3D+TOF 4i10s
Gaussian filter 8
Injected dose
Rubidium chloride (82Rb) Injection
Rest: 20 mCi (740 MBq)
Stress: 20 mCi (740 MBq)
CT Scan parameters
80 kV/30 ref mAs
82Rubidium has a 75-second half-life and is produced by using an 82Sr/82Rb generator. The generator is relatively small, allowing imaging centers to use and store on-site. The access to and ease of using this radiopharmaceutical allows for broader use of this technology compared to ammonia N 13 . The generator can be eluted every ten minutes, allowing quicker scanning and faster exam times than with ammonia PET or Technetium-99m (99mTc) SPECT MPI Imaging.22
In 1954 82Rb was discovered to have similar behavior to potassium, with uptake in the myocardial muscle proportional to blood flow in coronary arteries.23 A number of 82Rb/PET clinical studies performed from 1954 to the 80’s displayed excellent diagnostic accuracy compared to 99mTc/SPECT, leading to FDA approval of the first 82Sr/82Rb generator in 1989.23
As the number of PET systems in the US grew, improved strontium 82 production led to a vast increase in the use of 82Sr/82Rb generator. There are advantages of using 82Rb over that of 99mTC SPECT imaging such as the high prognostic value of quantification, accurate measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR), and a lower effective dose in adults.23 In addition, 82Rb has improved diagnostic accuracy in women with large breasts and obese patients with a body mass index >30 kg.23
Comparing the two radiopharmaceuticals in a meta-analysis and along certain metrics, 82Rb is revealed to be superior to 99mTc for MPI.
Results of meta-analyses with 82Rb PET compared to that of 99mTc SPECT25
Important safety information
“Heart Disease Facts.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 15 July 2022, https://www.cdc.gov/heartdisease/facts.htm.
“Stroke Facts.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 5 Apr. 2022, https://www.cdc.gov/stroke/facts.htm.
Skali, Hicham et al. “18F-FDG PET/CT for the assessment of myocardial sarcoidosis.” Current cardiology reports vol. 15,4 (2013): 352.
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Khan, Moien Ab et al. “Global Epidemiology of Ischemic Heart Disease: Results from the Global Burden of Disease Study.” Cureus vol. 12,7 e9349. 23 Jul. 2020, doi:10.7759/cureus.9349
“FDG PET for Myocardial Viability.” CMS.gov Centers for Medicare & Medicaid Services, https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?NCDId=298&NCDver=1.
Al Moudi, Mansour, and Zhong-Hua Sun. “Diagnostic value of (18)F-FDG PET in the assessment of myocardial viability in coronary artery disease: A comparative study with (99m)Tc SPECT and echocardiography.” Journal of geriatric cardiology : JGC vol. 11,3 (2014): 229-36. doi:10.11909/j.issn.1671-5411.2014.03.008
Medical Advisory Secretariat. “Positron emission tomography for the assessment of myocardial viability: an evidence-based analysis.” Ontario health technology assessment series vol. 5,16 (2005): 1-167.
Caobelli, Federico, et al. “The Importance of 18F-FDG Cardiac PET/CT for the Assessment of Myocardial Viability in Ischaemic Heart Disease.” Swiss Medical Weekly, EMH Media, 5 June 2021, https://smw.ch/article/doi/smw.2021.20511.
Caobelli, Federico, et al. “The Importance of 18F-FDG Cardiac PET/CT for the Assessment of Myocardial Viability in Ischaemic Heart Disease.” Swiss Medical Weekly, EMH Media, 5 June 2021, https://smw.ch/article/doi/smw.2021.20511.
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Celiker-Guler E, Ruddy TD, Wells RG. Acquisition, Processing, and Interpretation of PET 18F-FDG Viability and Inflammation Studies. Curr Cardiol Rep. 2021;23(9):124. Published 2021 Jul 16. doi:10.1007/s11886-021-01555-7
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Yoshinaga, Keiichiro, et al. “Generator-Produced Rubidium-82 Positron Emission Tomography Myocardial Perfusion Imaging-from Basic Aspects to Clinical Applications.” Journal of Cardiology, Elsevier, 8 Feb. 2010, https://www.sciencedirect.com/science/article/pii/S0914508710000109#tbl1.
Nakazato R, Berman DS, Alexanderson E, Slomka P. Myocardial perfusion imaging with PET. Imaging Med. 2013;5(1):35-46. doi:10.2217/iim.13.1
Maddahi J, Packard RR. Cardiac PET perfusion tracers: current status and future directions. Semin Nucl Med. 2014;44(5):333-343. doi:10.1053/j.semnuclmed.2014.06.011
Fathala A, Aboulkheir M, Shoukri MM, Alsergani H. Diagnostic accuracy of 13N-ammonia myocardial perfusion imaging with PET-CT in the detection of coronary artery disease. Cardiovasc Diagn Ther. 2019;9(1):35-42. doi:10.21037/cdt.2018.10.12
Widening the Availability of Ammonia to Increase the Footprint of ... https://link.springer.com/content/pdf/10.1007/s12350-019-01986-4.pdf.
“Rubidium 82.” Rubidium 82 - an Overview | ScienceDirect Topics, https://www.sciencedirect.com/topics/medicine-and-dentistry/rubidium-82.
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