European Nuclear Medicine Guide
[18F]-Fluoro-2-deoxy-2-d-glucose, also known as:
[18F]-Fluorodeoxyglucose
[18F]-FDG
FDG
FDG is a glucose analogue. This tracer is transported into cells by glucose transporters (GLUT) expressed on the cell membrane. Once inside the cell, FDG is phosphorylated by the enzyme hexokinase and becomes trapped.
To minimize physiological uptake of this tracer in the heart, a stringent cardiac preparation protocol is recommended. This includes consuming a low-carbohydrate/high-fat meal and undergoing a prolonged fasting period prior to the test. These steps help suppress physiological myocardial glucose uptake and enhance FDG uptake in macrophage-dense regions.
Under normal conditions, cardiac myocytes utilize both free fatty acids (FFA) and glucose as energy sources, whereas inflammatory cells primarily rely on glucose. To differentiate normal myocardium from inflamed myocardium and to enhance FDG uptake in macrophage-rich regions, FDG PET relies on the suppression of physiological FDG (glucose analogue) uptake [19].
Pre-imaging preparation involves adhering to a high-fat, low-carbohydrate diet for 24 hours prior to scanning to minimize dietary glucose-related competitive inhibition of FDG uptake [20].
To assess the presence of cardiac involvement in clinically manifest cardiac sarcoidosis using cardiac FDG PET-CT.
Pregnancy is a relative contra-indication. It is not recommended to interrupt breastfeeding [19].
Cardiac sarcoidosis (CS) is a multisystem inflammatory disorder of unknown etiology, 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 it could be the method of choice for identifying the active inflammatory phase of CS and in the monitoring and modifying of immunosuppressive treatment.
Histological confirmation can be made by endomyocardial biopsy (EMB). However, its [21,22]. This can be improved to 50% if intracardiac voltage mapping, FDG-PET, or Cardiac Magnetic Resonance imaging (CMR) guided biopsy is performed [21-23]. Furthermore, EMB can cause errors and complications, such as myocardial perforation.
Other reasons for uptake on 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 (2-4 MBq/kg).
The effective dose per administered activity is 19 µSv/MBq [19]. The range of the effective doses for the suggested activities is: 3.5-7.6 mSv.
Caveat:
It should be noted that the quantity “Effective Dose” does not necessarily reflect the radiation risk associated with this nuclear medicine examination. If the risk associated with the procedure is to be assessed, it is mandatory to adjust the radiation-associated risk factors at least according to the gender and age distribution of the institution’s patient population.
CAD should be excluded first as this may interfere with the assessment of the scans. 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 (Table 1):
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 including end stage cardiac sarcoidosis.
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 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.
Table 1: shows the patterns seen in a CS test: Line 1 and 2 are subtypes of the same pattern (see text).
After evaluating myocardial perfusion and inflammatory images, extra-cardiac structures should also be assessed for areas of sarcoidosis involvement as well as incidental findings, and these should be included in the final report.
Current available evidence confirms the prognostic value of FDG-PET. Patients with abnormal FDG uptake had higher odds of major adverse cardiac events, including sustained ventricular tachycardia and sudden cardiac death (OR 3.12, CI 1.9–5.01 p < 0.00001) as compared to known or suspected CS patients with normal FDG-PET [24].
Focal right ventricular uptake was shown to be an independent predictor of major adverse cardiac events (OR 5.24, CI 1.1–25.1, p = 0.04) [24,25].
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 myocytes, and this is particularly evident with prolonged fasting of up to 18 hours [26]. The effectiveness of prolonged fasting is increased with a diet consisting of high fat and low carbohydrates.
Another potential tool 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 [27].
Expert consensus has proposed two possible options for dietary preparation of patients with known or suspected CS prior to FDG PET [28].
The first includes dietary manipulation with at least two high-fat (>35 g) low-carbohydrate (<3 g) meals the day before the test, followed by 4–12 h fast. For those unable to perform dietary manipulation, 18 h of fasting is recommended as an alternative. While several groups have shown that dietary manipulation is superior to prolonged fasting [29] many patients struggle to complete this preparation due to complexity, difficulty with food label understanding, and dietary restrictions.
Dietary preparation of diabetic patients remains challenging. Insulin-dependent diabetic patients should continue only basal insulin and reduce or stop rapid-acting insulin. If needed, a sliding scale may be achieved the day before but not the day of the study [28]. For non–insulin-dependent patients, oral hypoglycemic 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 as described above. 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 60-minute or 90-minute after the injection, followed by a 10 minute to 30-minute non-gated acquisition [30].
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 should rather be extended from the base of the skull to the upper thigh, considering the patient’s clinical information.
In 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 of PET/CT can be reoriented into the standard cardiac views (short axis, horizontal long axis, vertical long axis) in a similar way to perfusion images.