European Nuclear Medicine Guide
[18F]FDG is a glucose analogue. Glucose metabolism is generally enhanced in tumours. Transport into cells is mediated by the GLUT expressed on the cell membrane. Once inside the cell, [18F]FDG is phosphorylated by the enzyme hexokinase and trapped. This mechanism of uptake is counteracted by the activity of the enzyme glucose 6-phosphatase, which dephosphorylates FDG allowing it to exit the cell.
In primary brain tumours, [18F]FDG can be used for tumour grading and biopsy targeting, since the degree of [18F]FDG uptake reflects the aggressiveness of the disease and tumour cell density. Consequently, [18F]FDG PET can also provide prognostic information. There are not enough data supporting the use of [18F]FDG PET to discriminate glioma recurrence from post-treatment changes. In previously irradiated brain metastases, [18F]FDG can be used for differential diagnosis between tumour recurrence and radionecrosis.
A recent meta-analysis has shown relatively good performances of [18F]FDG for discriminating between low- (LGG) and high- (HGG) grade gliomas: for a mean tumour-to-background ratio (TBR) ≥ 1.4 or maximum TBR ≥ 1.8, sensitivity, specificity and accuracy were 60%, 91% and 74%, respectively.
In contrast, relatively poor performances were shown for discriminating between tumoural and non tumoural lesions (sensitivity = 38%; specificity = 86%) and between glioma and non-glioma lesions (sensitivity = 35%; specificity = 65%).
In general, in accordance with the recent RANO/EANO recommendations for PET imaging in gliomas, FDG should be used only if amino acids (i.e., [11C]methionine, [18F] FET, [18F]FDOPA) are unavailable, because these show better diagnostic performances.
In previously irradiated brain metastases, [18F]FDG PET can be considered as a good alternative to amino acids with sensitivity and specificity ranging between 80-90% in the differential diagnosis between tumour progression and radionecrosis using delayed acquisition (2-4 h after tracer injection).
The suggested activities to administer for adults range from 150-250 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 14 MBq.
The effective dose per administered activity is 19 µSv/MBq [3]. The range of the effective doses for the suggested activities is: 2.9-4.8 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."
For correct [18F]FDG PET image interpretation in brain tumours, correlation with MRI is strongly recommended. FDG uptake is physiologically high in the brain, especially in cortical areas, leading to a poor tumour to background contrast. There are no standardized criteria for image interpretation which essentially depends on the clinical question. Qualitative comparison with the surrounding background may suffice for distinguishing between LGG and HGG. Uptake of LGG is generally lower than that of the surrounding background, while uptake of HGG is higher. It is good practice, however, to provide a quantification of TBR to facilitate intra-patient and inter-patient comparison.
In the setting of previously irradiated secondary lesions, [18F]FDG uptake should be abolished within the field of irradiation, therefore any significant increase of uptake above the background can be considered suggestive for disease recurrence. Acquisition of late time point images might increase the accuracy of tumour detection and can help the differential diagnosis in case of post-treatment changes.
[18F]FDG uptake is not specific for tumours; increased [18F]FDG uptake can be seen in several non-oncological conditions (e.g. inflammation/infection, epilepsy etc.). [18F]FDG uptake is decreased by corticosteroids, therefore images should be interpreted with caution in case of concurrent treatment with this class of drugs.
Patients should fast for at least 4 h prior to injection. Nevertheless, in brain tumours hyperglycaemia does not need to be corrected. If deemed necessary, mild sedatives (e.g. benzodiazepines) can be given to increase the patient’s comfort.
Detailed procedural guidelines are available in the EANM procedure guidelines for PET brain imaging using [18F]FDG, version 2 [60]. Further information can be found in the published literature [61–68].