European Nuclear Medicine Guide
FDG is a glucose analogue. Transport into cells is mediated by the glucose transporters (GLUT) expressed on the cell membrane. Once inside the cell, FDG is phosphorylated by the enzyme hexokinase and trapped. The myocardium can quickly adapt to changing environments by switching its energy source to the most efficient: fatty acids are preferred under fasting and aerobic conditions. Since fatty acid metabolism is highly oxygen dependent, the myocardium will quickly switch to glucose metabolism in ischemic conditions. Stunned and hibernating myocardial tissue still have intact cells, and even in low blood flow (ischemic conditions), these cells will take up FDG in comparable or even greater amount than healthy, normal myocardial tissue.
Assessment of myocardial viability in patients considered for revascularization in order to predict outcome benefit, for correct stratification and to guide further treatment.
Pregnancy is a relative contra-indication. Interrupt breastfeeding for 3 to 6 hours after the administration of dose. Breast milk could be collected and stored beforehand, in order to be provided to the infant during the interruption period [15].
The assessment of myocardial viability has been an important prerequisite in the decision-making regarding revascularization. This central role of myocardial viability assessment was supported by observational studies and meta-analyses showing that after revascularization patients with myocardial viability had a better outcome compared to those without myocardial viability. Acknowledging that prospective outcome data are limited, viability testing still has a role in complex patients who are at the highest risk of adverse events from revascularization. In this scenario an objective measurement of viability can tip the balance in favour of medical therapy or revascularization. Myocardial viability testing will continue to play a role in revascularization decision making, although larger randomized trials with clinical outcome end-points are needed to further define its role.
Based on these data, the guidelines for myocardial revascularization state that myocardial revascularization should be considered in presence of viable myocardium (Class IIa, level B) [16].
The suggested activities to administer for adults range from 185 MBq to 400 MBq. In paediatric nuclear medicine, the activities should be modified according to the EANM paediatric dosage card (https://www.eanm.org/publications/dosage-calculator/). The minimum recommended activity is 26 MBq.
The effective dose per administered activity is 19 µSv/MBq [3].The range of the effective doses for the suggested activities is: 3.5-7.6 mSv.
Caveat
Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."
Four image patterns emerge when metabolic images are compared to perfusion images:
Caution is advised when SPECT perfusion images are compared to PET metabolic images, because these different techniques might display different artefacts (typical breast or diaphragm attenuation artefacts in SPECT).
To ensure that the myocardium will preferentially use glucose instead of fatty acids, a strict preparation is required.
The evening preceding the investigation, a low-fat meal should be consumed. In the morning, a low fat/no fat and high carbohydrate breakfast is allowed. Patients should be advised not to use milk or creamer in their coffee or tea. In contrast to FDG imaging in oncology or inflammation, sugar is allowed. Several options exist to further reduce the amount of free fatty acids and to promote myocardial glucose metabolism.
Acipimox
Acipimox, a nicotinic acid derivative, is used to lower free circulating fatty acid levels. By adding a low fat/high carbohydrate meal, insulin levels will rise and promote the use of glucose by the myocardium. With this method, myocardial FDG uptake can reach similar levels compared to the more cumbersome euglycemic clamping method. The acipimox method is commonly used but acipimox is not available for clinical use in all countries. A protocol can consist of the administration of 2 capsules of 250 mg acipimox 30 min apart, followed by a carbohydrate rich meal (e.g. white bread with jam, without butter, coffee with sugar, juice) 30 min later. One hour after the second acipimox capsule, FDG can be administered. Imaging is started 45 min after FDG injection.
Flushing is a common side effect of acipimox, and this can be prevented by administering 500 mg acetylsalicylic acid (aspirin). In diabetic patients, a short acting insulin can be added shortly before FDG administration.
Euglycemic hyperinsulinemia clamping
This method consists of a continuous (preceding, during, and after FDG administration) and simultaneous infusion of both glucose and insulin to maximize glucose, and thus FDG, uptake in the myocardium. To prevent hypopotassaemia, KCl is added to the infusion. During infusion, monitoring of blood glucose levels is required to adjust infusion speed accordingly. This method results in high insulin levels and consequently excellent image quality in both diabetic and non-diabetic patients, it is, however, labour intensive and time consuming. A less extensive version of this method using a 30 min glucose-insulin- potassium infusion has also been reported to result in excellent image quality.
Oral glucose loading
Promoting cardiac glucose uptake can be achieved by administering 25-100 g glucose per os, sometimes with the addition of intravenous insulin. This method will often result in suboptimal images and up to 10% uninterpretable scans. Certainly, in diabetic patients, this method will not lead to sufficient cardiac FDG uptake.
Usually, myocardial viability imaging is done in combination with a form of perfusion imaging, which may even be done the same day using Technetium-99m, Rubidium-82 or other perfusion tracers. Acquisition can be started 45 min after tracer injection.
Images are acquired in supine position preferably with both arms above the head. The heart will usually fit in a single bed position. Acquisition time depends on the injected dose and camera parameters. Scan times vary between 10 and 30 min. Optionally, ECG gated images can be acquired. However, perfusion images will usually already provide information on LV function.
In the hybrid PET/CT systems, a CT scan should be obtained to provide attenuation correction. Depending on the CT, these images can be used for anatomical reference. In advanced CT systems with at least 64 slices, even a CT coronary angiography can be added to the investigation providing information on the presence and extent of coronary artery stenosis. This anatomical information might be helpful in the overall interpretation of the images.
Images should be reviewed prior to the patient leaving the department. In case of high blood pool activity, images should be reacquired after administration of additional insulin. Artefacts may be caused by patient motion during acquisition or between PET and CT imaging. Reacquisition might be necessary.
The acquired data is reoriented into the standard cardiac views (short axis, horizontal long axis, vertical long axis) in a similar fashion to perfusion images. Several software packages are available to analyse and segment these images and provide quantified data on the extent of metabolic defects, also in comparison to perfusion images.