European Nuclear Medicine Guide
FDG is a glucose analogue. This tracer is transported into cell by the glucose transporters (GLUT) expressed on the cell membrane. After entering the cell, FDG is phosphorylated by the enzyme hexokinase and then trapped.
Due to the presence of physiologic uptake of this tracer in the heart, it is recommended to perform a stringent cardiac protocol of low carbohydrate/high fat meal and prolonged fast pre-test to suppress physiological myocardial glucose uptake and to maximise FDG uptake in macrophage-dense regions.
To determine the presence of cardiac involvement with clinically manifest cardiac sarcoidosis using cardiac FDG PET-CT.
Pregnancy is a relative contra-indication. It is not recommended to interrupt breast feeding [1].
Cardiac sarcoidosis (CS) is a multisystem inflammatory disorder of unknown aetiology, characterized by the presence of non-caseating granulomas. The spectrum of disease manifestations in CS is highly variable from asymptomatic patients to presentation with heart block, ventricular arrhythmia, left ventricular dysfunction and sudden cardiac death.
FDG PET/CT seems to be particularly useful in the differential diagnosis of cases where conventional imaging is non-diagnostic, equivocal or contra-indicated (as cardiac MRI in patients with implantable cardiac device). Indeed, FDG PET/CT scans can help to identify occult diagnostic biopsy sites and to evaluate the activity of inflammation. We have to remind that myocardial biopsy has a low sensitivity due to the patchy distribution of the granulomas in CS and can cause errors and complications, such as myocardial perforation.
False-positive uptake in FDG PET/CT can be observed in patients with other granulomatous diseases, infections, and neoplasms.
The suggested activities to administer for adults range from 185 MBq to 400 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."
In order to obtain an accurate interpretation of the images of inflammatory state by using FDG PET/CT, it is recommended to scan the patient with myocardial perfusion imaging (MPI) performing SPECT/CT scintigraphy with:
-[99mTc]Tc-2-methoxyisobutylisonitrile ([99mTc]Tc-sestamibi)
-[99mTc]Tc-1,2-bis[bis(2-ethoxyethyl)phosphino]ethane ([99mTc]Tc-tetrofosmin)
or PET/CT with:
-[82Rb]rubidium chloride (Rubidium-82)
-[13N]ammonia
Indeed, a resting myocardial perfusion defect could be due to microvascular compression from inflammation or may be due to scar.
Four image patterns emerge when FDG PET/CT images are compared to MPI:
-MPI abnormal/normal + patchy cardiac FDG uptake: cardiac sarcoidosis manifests as patchy or focal on diffuse FDG uptake, which may or may not have correspondent myocardial perfusion abnormalities. Care should be taken in presence of focal FDG accumulation surrounding implantable cardiac device as pathologic or in presence of isolated lateral FDG uptake, which may be a non-specific finding;
-MPI abnormal + no cardiac FDG uptake: a myocardial perfusion defect is present in a ventricular wall or segment on MPI without corresponding pathologic FDG myocardial uptake consistent with scar from prior ischemic or non-ischemic disease;
-MPI normal+ blood pool FDG uptake: no perfusion defects are visualized on MPI study. FDG is present only in the blood pool with no myocardial uptake, consistent with effective suppression of physiologic myocardial glucose accumulation and a normal study;
- MPI normal+ diffuse myocardial FDG uptake: no perfusion defects are visualized on MPI images. There is a diffuse uptake of 18F-FDG throughout the entire myocardium with or without areas of focal on diffuse uptake. These findings are nonspecific and are due to ineffective suppression of physiologic myocardial glucose uptake.
After assessment of the myocardial perfusion and inflammatory images, extra-cardiac structures should be evaluated for both areas of sarcoidosis involvement and for incidental findings and included in the final report.
Optimal and strict patient preparation is required when using FDG PET/CT to evaluate for CS to suppress physiological glucose uptake by the myocardium. During the fasting state, lipids become the preferential substrate for myocyte, and this is particularly evident with prolonged fasting of upward of 18 hours [19]. The effectiveness of prolonged fasting state is increased with a diet consisting of high fat and low carbohydrates.
Another potential tool in order to increase serum free fatty acid levels is via the use of unfractionated heparin (typically administered dose is 50 U/kg approximately 15 minutes prior to 18F-FDG administration), which stimulates lipolysis and could increase free fatty acid levels without prolonging the partial thromboplastin time [20].This protocol can be combined with the fasting and a high fat and low carbohydrates diet.
Unfortunately, it is not been identified an optimal dietary preparation for diabetic patients. Insulin-dependent diabetic patients should continue basal insulin with the reduction of rapid-acting insulin. If needed, a sliding scale may be achieved the day before but not the day of the study [21]. For non–insulin-dependent patients, oral hypoglycaemic drugs should be avoided during periods of prescribed fasting.
Usually CS imaging is done in combination with myocardial perfusion imaging (MPI), which may even be done the same day using technetium-99m, rubidium-82 or other perfusion tracers. MPI is performed with a gated study for providing information on left ventricular function, such as ejection fraction and regional wall motion abnormalities.
The inflammatory myocardial state is studied with FDG PET/CT, performed approximately a 60 minute to 90 minute uptake period after the injection, followed by a 10 minute to 30 minute non-gated acquisition [22].
Images are acquired in supine position preferably with both arms above the head. The field of view for the inflammation acquisition scan may be focused on the heart alone in a single bed position, or may be extended to include base of the skill to the upper thigh.
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. The acquired data is reoriented into the standard cardiac views (short axis, horizontal long axis, vertical long axis) in a similar way to perfusion images.