An interindividual comparison of O-(2- [(18)F]Fluoroethyl)-L-Tyrosine (FET)- and L-[Methyl-(11)C]Methionine (MET)-PET in patients with brain gliomas and metastases
L-[methyl-(11)C]methionine (MET)-positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of (11)C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is labeled with (18)F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI).
We examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion-to-gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up.
There was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p < 0.001), respectively. Image contrast was similar for MET- and FET-PET (lesion-to-gray matter ratios of 2.36 ± 1.01 and 2.33 ± 0.77, respectively). Mean GTV in 17 glioma patients was not significantly different on MET- and FET-PET. Both MET- and FET-PET delineated tumor tissue outside of MRI changes. Both tracers provided differentiated tumor tissue and treatment-related changes with a sensitivity of 91% at a specificity of 100%.
O-(2-[(18)F]fluoroethyl)-L-tyrosine-PET and MET-PET provide comparable diagnostic information on gliomas and brain metastases. Like MET-PET, FET-PET can be used for differentiation of residual or recurrent tumor from treatment-related changes/pseudoprogression, as well as for delineation of gliomas.
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- "F-fluoro-ethyl-L-tyrosine (FET) may be more specific for brain tumor tissue. Although they provide comparable diagnostic information, the short half-life of MET (20 min) requires a cyclotron on site (Grosu et al., 2011). FET (half-life 120 min) does not have this limitation , which makes it more practical in the clinical setting (Rapp et al., 2013). "
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ABSTRACT: Functional imaging studies complement structural magnetic resonance imaging (MRI) in the assessment of patients with brain tumor-associated focal epilepsy. (11) C-Methionine (MET) and (18) F-fluoro-ethyl-l-tyrosine (FET) are amino acid analogues that highlight metabolically active areas in positron emission tomography (PET). Ictal single photon emission computed tomography (SPECT) can provide information about perilesional areas of seizure onset and early propagation. Functional MRI (fMRI) and diffusion tensor imaging (DTI) allow noninvasive identification of potentially eloquent motor, sensory, and language cortical areas and pathways with an accuracy of 10-15 mm compared to electrocortical stimulation (ECS). Repetitive navigated transcranial magnetic stimulation (TMS) allows even more precise noninvasive delineation of primary motor cortex. Information from functional imaging studies helps in the planning of brain tumor biopsies, resections, and the planning of intracranial video-electroencephalography (EEG) studies.
Available from: N. Jon Shah
- "O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) has become a well- established 18 F-labelled amino acid for PET (half-life, 110 min) that shows logistic advantages for clinical practice compared with the short lived L-Methyl-[ 11 C]-methionine ( 11 C-MET) (half-life 20 min)    . Clinical results in brain tumors with PET using 11 C-MET and 18 F-FET have been reported to be very similar   . Although the uptake of radioactive amino acids is considered relatively specific for neoplastic masses, the possibility of non-specific enhancement must be borne in mind. "
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PET using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) allows improved imaging of tumor extent of cerebral gliomas in comparison to MRI. In experimental brain infarction and hematoma, an unspecific accumulation of (18)F-FET has been detected in the area of reactive astrogliosis which is a common cellular reaction in the vicinity of cerebral gliomas. The aim of this study was to investigate possible (18)F-FET uptake in the area of reactive gliosis in the vicinity of untreated and irradiated rat gliomas.
F98-glioma cells were implanted into the caudate nucleus of 33 Fisher CDF rats. Sixteen animals remained untreated and in 17 animals the tumor was irradiated by Gamma Knife 5-8 days after implantation (2/50 Gy, 3/75 Gy, 6/100 Gy, 6/150 Gy). After 8-17 days of tumor growth the animals were sacrificed following injection of (18)F-FET. Brains were removed, cut in coronal sections and autoradiograms of (18)F-FET distribution were produced and compared with histology (toluidine blue) and reactive astrogliosis (GFAP staining). (18)F-FET uptake in the tumors and in areas of reactive astrocytosis was evaluated by lesion to brain ratios (L/B).
Large F98-gliomas were present in all animals showing increased (18)F-FET-uptake which was similar in irradiated and non-irradiated tumors (L/B: 3.9 ± 0.8 vs. 4.0 ± 1.3). A pronounced reactive astrogliosis was noted in the vicinity of all tumors that showed significantly lower (18)F-FET-uptake than the tumors (L/B: 1.5 ± 0.4 vs. 3.9 ± 1.1). The area of (18)F-FET-uptake in the tumor was congruent with histological tumor extent in 31/33 animals. In 2 rats irradiated with 150 Gy, however, high (18)F-FET uptake was noted in the area of astrogliosis which led to an overestimation of the tumor size.
Reactive astrogliosis in the vicinity of gliomas generally leads to only a slight (18)F-FET-enrichment that appears not to affect the correct definition of tumor extent for treatment planning.
Available from: Irina Götz
- "PET-tracers currently used for imaging of brain tumors are mostly radio labeled amino acid (AA) tracers. These AA are preferentially taken up by tumor cells (Derlon et al., 1989; Heiss et al., 1999; Grosu et al., 2011) due to an overexpression of amino acid transporters, while the uptake of the normal brain tissue is relatively low. It has been demonstrated that AA uptake in tumor tissue is almost entirely mediated by type l-AA carriers (Heiss et al., 1999). "
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ABSTRACT: In the treatment of patients suffering from malignant glioma, it is a paramount importance to deliver a high radiation dose to the tumor on the one hand and to spare organs at risk at one the other in order to achieve a sufficient tumor control and to avoid severe side effects. New radiation therapy techniques have emerged like intensity modulated radiotherapy and image guided radiotherapy that help facilitate this aim. In addition, there are advanced imaging techniques like Positron emission tomography (PET) and PET/CT which can help localize the tumor with higher sensitivity, and thus contribute to therapy planning, tumor control, and follow-up. During follow-up care, it is crucial to differentiate between recurrence and treatment-associated, unspecific lesions, like radiation necrosis. Here, too, PET/CT can facilitate in differentiating tumor relapse from unspecific changes. This review article will discuss therapy response criteria according to the current imaging methods like Magnet resonance imaging, CT, and PET/CT. It will focus on the significance of PET in the clinical management for treatment and follow-up.
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