Cardiac PET - Explore cardiological indications in PET and PET/CT

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


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:

Fludeoxyglucose F 18 Injection 
(18F FDG)

Cyclotron-produced and the most widely available 
radiopharmaceutical; indicated in assessing 
myocardial hibernation (also known as myocardial viability)

Ammonia N 13 Injection 

Indicated for MPI due to a 10-minute half-life; requires a cyclotron on-site or within 30 minutes of the imaging center


Generator-produced radiopharmaceutical indicated
for MPI


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

Pooled Sensitivity of 18F FDG PET9





Prediction of improved regional left 
ventricular function after 





Prediction of an improvement of the 
global left ventricular function




















Dobutamine stress echocardiography (DSE)





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

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.

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

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:

Key differences of 82Rb and Ammonia N 1317,21


Ammonia N 1317,21


76 sec

9.97 min

Positron range

2.60 mm

0.57 min

Exam time

30 min

70 min

First-pass cardiac extraction fraction



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.

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.




Patient-based sensitivity23

Patient-based specificity23

82Rb PET



0.91 (0.85-0.96)

0.90 (0.75-1.00)




0.88 (0.81-0.90)

0.67 (0.61 – 0. 82)

Important safety information

Fludeoxyglucose F 18 

Indications & usage

Fludeoxyglucose F 18 Injection (18F FDG) is indicated for positron emission tomography (PET) imaging in the following settings:

  • Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.
  • Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.
  • Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures.

Important safety information

  • Radiation Risk: Radiation-emitting products, including Fludeoxyglucose F18 Injection, may increase the risk for cancer, especially in pediatric patients. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker.
  • Blood Glucose Abnormalities: In the oncology and neurology setting, suboptimal imaging may occur in patients with inadequately regulated blood glucose levels. In these patients, consider medical therapy and laboratory testing to ensure at least two days of normoglycemia prior to Fludeoxyglucose F 18 Injection administration.
  • Adverse Reactions: Hypersensitivity reactions with pruritus, edema, and rash have been reported. Have emergency resuscitation equipment and personnel immediately available.

Dosage forms and strengths

Multiple-dose 30 mL and 50 mL glass vial containing 0.74 to 7.40 GBq/mL (20 to 200 mCi/mL) Fludeoxyglucose F 18 Injection and 4.5 mg of sodium chloride with 0.1 to 0.5% w/w ethanol as a stabilizer (approximately 15 to 50 mL volume) for intravenous administration.

Fludeoxyglucose F 18 Injection is manufactured and distributed by:
PETNET Solutions, Inc.
810 Innovation Drive
Knoxville, TN 39732

These highlights do not include all the information needed to use Fludeoxyglucose F 18 Injection safely and effectively. 

Ammonia N 13

Indications & usage

Ammonia N 13 Injection (13NH3) is a radioactive diagnostic agent for positron emission tomography (PET) indicated 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.

Important safety information

  • Cancer Risk: Ammonia N 13 Injection may increase the risk of cancer. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and the health care worker.
  • Adverse Reactions: No adverse reactions have been reported for Ammonia N 13 Injection based on a review of the published literature, publicly available reference sources, and adverse drug reaction reporting systems. The completeness of the sources is not known.

Dosage forms and strengths

Glass vial (30 mL) containing 0.138-1.387 GBq (3.75-37.5 mCi/mL) of Ammonia N 13 Injection in aqueous 0.9 % sodium chloride solution (the total volume in the vial will vary) for intravenous administration.

Ammonia N 13 Injection is manufactured and distributed by:
PETNET Solutions, Inc.
810 Innovation Drive
Knoxville, TN 39732

These highlights do not include all the information needed to use Ammonia N 13 Injection safely and effectively.