European Nuclear Medicine Guide
O-(2-[18F]fluoroethyl)-L-tyrosine also known as:
[18F]-FET
FET
[18F]-FET is a radiolabelled amino acid analogue specifically designed for imaging of glioma. It is transported across the blood-brain barrier and into cells primarily via the L-type amino acid transporter system (LAT1 and LAT2). Unlike natural amino acids, [18F]-FET is not incorporated into proteins and shows low uptake in inflammatory cells, making it highly specific for tumour imaging. The pathophysiological rationale for PET imaging with [18F]-FET in brain tumours is based on increased amino acid transport in tumour cells due to overexpression of LAT1 and LAT2. This overexpression is associated with tumour proliferation and infiltration. Unlike [18F]-FDOPA, [18F]-FET is not metabolized, has low uptake in basal ganglia and provides a more direct measurement of amino acid transport [401].
[18F]-FET is indicated for use with PET in adults and paediatric patients for [402, 403]:
Primary diagnosis:
Determination of the tumour extent and infiltration
Assessment of the tumour grade
Selection of optimal biopsy site
Treatment planning:
o Delineation of the tumour borders for radiotherapy planning
o Guidance for surgical resection
Monitoring:
o Assessment of treatment response
o Early detection of tumour recurrence
o Differentiation between tumour recurrence and post-therapeutic changes
Pregnancy is considered a relative contraindication, although the radiation dose to the foetus would be below the threshold for deterministic effects. Breastfeeding should be interrupted for 4 hours after administration of radiopharmaceuticals.
[18F]-FET PET imaging has demonstrated impressive diagnostic accuracy in neuro-oncological applications, achieving sensitivity rates of 80–90% in detecting primary brain tumours, with particularly notable success in identifying high-grade gliomas. It excels in distinguishing tumour recurrence from post-treatment radiation necrosis, with documented specificity rates of 85–95% — a significant improvement over conventional diagnostic methods [402, 403]. When compared to standard magnetic resonance imaging, PET shows superior accuracy in differentiating true tumour progression from treatment-related changes in brain tissue.
The dynamic imaging capabilities of PET provide essential quantitative metrics for tumour characterization. Time-activity curves generated from dynamic acquisitions offer valuable diagnostic insights through radiotracer kinetic analysis. Parameters such as early slope characteristics and time-to-peak measurements correlate strongly with tumour grade and biological behaviour [405]. This kinetic analysis has proven particularly valuable in evaluating recurrent gliomas, where these quantitative measures significantly enhance diagnostic confidence and accuracy.
The clinical impact of PET imaging in neuro-oncological management has been substantial. Research shows that PET findings influence and change clinical decision-making in 30–50% of cases, significantly affecting therapeutic planning [406]. [18F]-FET PET imaging also enhances stereotactic biopsy accuracy by identifying metabolically active regions most likely to yield diagnostic tissue. In radiation therapy planning, PET data enables more precise target volume definition and optimal dose distribution. Most importantly, PET imaging allows earlier detection of tumour progression compared to conventional imaging methods, enabling more timely therapeutic interventions that may improve patient outcomes.
The recommended activities for adults are 185–200 MBq. In children, the activity should be calculated as a fraction of the activity for adults according to the child’s body weight using the factors provided by the EANM Paediatric Task Group [407]. The administered activity may be reduced in systems with higher sensitivity [412].
The effective dose for [18F]-FET is 16.5 µSv/MBq. (408) The urinary bladder wall receives the highest radiation exposure among all organs, with an absorbed dose of 53 μGy/MBq, making it the critical organ for this procedure. For a typical examination, patients can expect to receive a total effective dose of between 3.3 and 5.0 mSv [408]. The CT portion of the study will contribute additional radiation exposure, though the exact amount varies depending on the specific imaging protocol used for each patient.
The interpretation of 18F-FET PET imaging begins with a qualitative visual analysis, focusing on areas of increased tracer uptake compared to normal cortical activity in the contralateral hemisphere. A standardized three-tier grading system (mild, moderate, or intense) is used to classify uptake intensity relative to reference regions. A scan is considered positive when tracer accumulation clearly exceeds the background activity of the contralateral cortex.
In clinical interpretation, negative studies are particularly valuable in excluding high-grade neoplasms and significantly reducing the likelihood of oligodendroglial tumours. However, they have limited sensitivity for low-grade gliomas, especially those of astrocytic origin. While positive studies help to rule out benign pathology, they present challenges in definitive grade differentiation, as lower-grade lesions can sometimes demonstrate intense tracer uptake. Several factors require careful consideration during interpretation. These include physiological uptake in vascular structures (particularly near venous sinuses), blood-brain barrier disruption effects (whether from tumour infiltration or treatment), and potential false-positive findings following recent surgical interventions due to post-operative changes and inflammation [409].
For more objective assessment and longitudinal monitoring, semi-quantitative analysis methods are employed. These include standardized uptake value (SUV) calculations, both maximum and mean, and tumour-to-brain ratios (TBR), which compare lesional uptake to reference brain tissue. This standardization enables consistent interpretation across different examinations and institutions.
Dynamic acquisition analysis provides additional diagnostic insights through time-activity curves (TAC). Grade III/IV tumours typically show an early peak in mean ROI/VOI activity (within 20 minutes post-injection) followed by a plateau or decrease. In contrast, grade I/II gliomas often demonstrate continuously increasing uptake up to 40 minutes post-injection, though this pattern isn't specific and can also indicate treatment-induced changes such as radionecrosis or pseudoprogression [405].
Comprehensive guidelines for image interpretation and acquisition protocols can be found in the Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for glioma imaging using PET with radiolabelled amino acids and [18F]-FDG (version 1.0) [402]. Additional guidance for response assessment interpretation is available in the "PET-based response assessment criteria for diffuse gliomas (PET RANO 1.0)" published by the RANO group [410].
Before the procedure, patients should fast for at least 4 hours prior to receiving the injection. They may continue taking their regular prescribed medications as scheduled. Recent morphological imaging with MRI should be available for image fusion. During the image acquisition it is important for patients to remain relaxed and still, as excessive movement can affect the results [402].
The Joint EANM/EANO/RANO practice guidelines and SNMMI procedure standards for glioma imaging using PET with radiolabelled amino acids and [18F]-FDG (version 1.0) [402] provide comprehensive recommendations for acquisition protocols. For most neuro-oncological applications, standard static imaging is conducted 20–40 minutes after radiotracer administration, which provides optimal target-to-background contrast. In cases where kinetic analysis is recommended, dynamic acquisition protocols are implemented, capturing temporal tracer distribution patterns over a 0–40/50 minute post-injection period. The choice between static and dynamic acquisition approaches depends on the specific clinical indications and intended analytical methods.