European Nuclear Medicine Guide
Radiolabelled amino acids:
-(2-[18F]-fluoroethyl)- L-tyrosine, also known as:
● [18F]FET
● FET
3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine also known as:
● [18F]FDOPA
● [18F]fluorodopa
● FDOPA
[11C-methyl]- L -methionine also known as:
● [11C]methionine
● MET
anti-1-amino-3-[F-18]-fluorocyclobutane-1-carboxylic acid also known as:
● anti-3-[F-18] FACBC
● [18F]fluciclovine
Radiolabeled amino acids are transported into the cells by the Na+ - independent large neutral amino acid transporters, namely LAT1 and LAT2, which are over expressed on the tumour cell surface. This mechanism is independent from blood brain barrier permeability. Radiolabelled amino acids MET, FET and FDOPA have different selectivity for LAT1 or LAT2, however, no relevant differences between available amino acids have been shown in terms of tumour detection. With the exception of MET, they are not incorporated into protein biosynthesis. FDOPA is a substrate for the enzyme aromatic amino acid decarboxylase in dopaminergic neurons; therefore, uptake by the basal ganglia is physiological. [18F]fluciclovine is a synthetic amino acid analogue, whose intracellular transport is primarily mediated by system ASC-amino acid transporters, especially ASCT2.
In primary brain tumours, amino acid PET is indicated for:
● differentiation between neoplastic and non-neoplastic tissue;
● delineation of tumour extent;
● biopsy targeting;
● surgery planning;
● radiotherapy planning;
● verification of resection extent;
● diagnosis of treatment-induced changes versus relapse;
● treatment monitoring and follow up.
Notably, these indications are established in gliomas in accordance with the RANO/EANO recommendations and might not necessarily apply to other histological subtypes. In previously irradiated brain metastases, amino acids are indicated for differential diagnosis between tumour recurrence and radionecrosis.
There are no absolute contraindications to the administration of radiolabeled amino acids.
In case of pregnancy, the benefits of undergoing an amino acid PET scan should be balanced against the potential harm to the foetus.
For MET, It is not recommended to interrupt breast feeding [1].
In primary brain tumours, amino acid PET provides additional information over standard MRI, particularly in delineation of true tumour extent, as well as in treatment monitoring and response assessment, including differential diagnosis between treatment-related changes and tumour recurrence.
Tumour grading is generally not accomplished with high performance.
In brain metastases, amino acid PET outperforms standard MRI in the differential diagnosis between progression and radionecrosis after stereotactic radiotherapy.
The suggested activities to administer for adults are:
18F]FET,[18F]fluorodopa and [18F]fluciclovine : 150-250 MBq
[11C]methionine: 200-250 MBq
No recommendations are given for paediatric nuclear medicine.
The effective doses per administered activity are [1]:
● [18F]FET: 16 µSv/MBq
● [18F]fluorodopa : 25 µSv/MBq
● [11C]methionine: 8.2 µSv/MBq
● [18F]fluciclovine: 22 µSv/MBq
The range of the effective doses for the suggested activities is: 2.4-6.3 mSv (fluorinated tracers) and 1.6-2.1 mSv for MET.
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."
It is strongly advised that amino acid images are interpreted in conjunction with MRI. Any increase of amino acid uptake above the background can be considered abnormal. However, unspecific amino acid uptake can be seen in inflammatory/demyelinating lesions, abscesses, ischemic lesions, vascular malformation, reactive astrocytosis, and hematomas. On the other hand, a significant proportion of LGG (10-30%) do not show increased amino acid uptake. Therefore, absence of increased uptake above the background does not exclude the presence of a neoplastic lesion. One specific pitfall of [18F]fluorodopa is the physiological striatal uptake which can interfere with tumour delineation in a non-negligible number of cases (10-15%).
When reporting amino acid PET, it is good practice to provide semi quantitative uptake measures (such as TBR or similar parameters) and their associated measurement times in order to facilitate intra-patient and inter-patient comparison as well as to allow for comparison with previous reports showing additional diagnostic/prognostic value of patient stratification based on uptake quantification.
Patients should fast for at least 4 h prior to injection. There are no additional specific indications to give. Premedication with carbidopa is not recommended prior to [18F]fluorodopa PET. Concurrent treatments have little influence on amino acid tumour uptake. If deemed necessary, mild sedatives (e.g. benzodiazepines) can be given to increase the patient’s comfort.
Detailed recommendations on standard procedures are available in the Joint EANM/EANO/RANO Practice guidelines/SNMMI Procedure Standards for Imaging of Gliomas Using PET With Radiolabelled Amino Acids and [18 F]FDG: Version 1.0. [37], as well as in the Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standard for PET imaging of brain metastases [38] The RANO group has also published PET-based response assessment criteria for diffuse gliomas (PET RANO 1.0 )[39]
Further details can be found in the published literature [30, 40-47].