18F-FET PET may be useful in the differential diagnosis between brain tumors and non-neoplastic lesions and between low-grade and high grade gliomas. Integration of 18F-FET PET into surgical planning allows better delineation of the extent of resection beyond margins visible with standard MRI. For biopsy planning, 18F-FET PET is particularly useful in identifying malignant foci within non-contrast-enhancing gliomas. 18F-FET PET may improve the radiation therapy planning in patients with gliomas. This metabolic imaging method may be useful to evaluate treatment response in patients with gliomas and it improves the differential diagnosis between brain tumours recurrence and post-treatment changes. 18F-FET PET may provide useful prognostic information in high-grade gliomas.

Based on recent literature data 18F-FET PET may provide additional diagnostic information compared to standard MRI in neuro-oncology 1).

For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference 2).

(18)F-Fluoroethyl-l-thyrosine (FET) is a positron emission tomography (PET) radiopharmaceutical applicable for widespread use because of its long half-life radionuclide.

Fluoroethyl Tyrosine Positron Emission Tomography for patients with gliomas undergoing multimodal treatment or various forms of irradiation is a powerful tool to improve the differential diagnosis 3).

FET PET reliably distinguishes between post-therapeutic benign lesions and tumour recurrence after initial treatment of low- and high-grade gliomas 4).

Maps of (18)FET uptake kinetics strongly correlated with histopathology in suspected grade II gliomas. Anaplastic foci can be accurately identified, and this finding has implications for prognostic evaluation and treatment planning 5).

Dynamic 18F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses 6).

In low grade gliomas 5 aminolevulinic acid fluorescence is the exception and FET PET is more sensitive. High grade areas in diffuse gliomas with anaplastic foci usually fluoresce, if they are FET PET positive. As a result, FET PET appears valuable for pre-operative identification of anaplastic foci and hot spots are strongly predictive for ALA-derived fluorescence, which highlight anaplastic foci during resection 7).

Age, tumor volume, and Fluoroethyl Tyrosine Positron Emission Tomography uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined 8).

47 patients were included in the study of whom 15 had confirmed glioma and seven had confirmed alternative diagnosis. 18F FET PET shows significantly higher uptake in high grade glioma than in non-glioma. Lesions with TBRmax >2.5 should be considered suspicious for glioma and biopsy considered. Threshold TBRmax > 3.0 is useful for differentiating high grade glioma from low grade glioma. This may be a particularly useful tool for directing management in eloquent areas, such as brainstem glioma 9).

Schebesch et al., from the University Medical Center Regensburg, Germany published five patients (3 female, 2 male; mean age 45.4 years) who underwent fluorescence-guided surgery for supratentorial, intracerebral lesions which showed no contrast-enhancement in the preoperative MRI but were, however, strongly suspicious for gliomas. Accordingly, all patients received a preoperative FET-PET scan and detailed histopathological workup was performed. After giving written informed consent, all patients received 5 mg/kg of FL at the induction of anesthesia. Surgery was conducted under white light and under the YELLOW 560 nm filter. They reviewed the surgical protocols, navigational storage and the image databases of our surgical microscopes for evidence of intraoperative fluorescence that corresponded to the FET-PET positive area.

In all patients they found distinct accordances between the FET-PET positive areas and the fluorescing regions within the targeted lesions. Histopathological workup of the fluorescent tissue revealed anaplastic oligodendroglioma, IDH-mutant and 1p/19-codeleted (WHO grade III) (n = 2), anaplastic astrocytoma, IDH-mutant (WHO grade III) (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade II) (n = 1) and pilocytic astrocytoma (WHO grade I) (n = 1). No adverse events were noted.

Despite the lack of gadolinium-enhancement in the preoperative MRI, all patients intravenously received FL to guide resection. Irrespective of the final grading, FL was extremely helpful in detecting the lesions and in identifying their border zones. In selected patients with NEG, but strong metabolic activity according to the FET-PET, FL may significantly increase the accuracy of surgery 10).

MRI and FET-PET were performed preoperatively and postoperatively in 62 patients undergoing 63 operations. FET-PET was performed in 43 cases within 72 hours after resection and in 20 cases >72 hours after resection. Detection and measurement of volume of residual tumors were compared. Correlations between residual tumor detection and timing of PET after resection and recurrence were examined.

Complete resection was confirmed by both imaging modalities in 44% of cases, and residual tumor was detected consistently in 37% of cases. FET-PET detected residual tumor in 14% of cases in which MRI showed no residual tumor. MRI showed residual tumors in 5% of cases that were not identified by PET. Average PET-based residual tumor volume was higher than MRI-based volume (3.99 cm(3) vs. 1.59 cm(3)). Detection of and difference in volume of residual tumor were not correlated with timing of PET after resection or recurrence status.

Postoperative FET-PET revealed residual tumor with higher sensitivity than MRI and showed larger tumor volumes. In this series, performing PET >72 hours after resection did not influence the results of PET. We recommend FET-PET as a helpful adjunct in addition to MRI for postoperative assessment of residual tumor 11).

Muoio B, Giovanella L, Treglia G. Recent Developments of 18F-FET PET in Neuro-oncology. Curr Med Chem. 2017 Nov 23. doi: 10.2174/0929867325666171123202644. [Epub ahead of print] PubMed PMID: 29173147.
Unterrainer M, Vettermann F, Brendel M, Holzgreve A, Lifschitz M, Zähringer M, Suchorska B, Wenter V, Illigens BM, Bartenstein P, Albert NL. Towards standardization of (18)F-FET PET imaging: do we need a consistent method of background activity assessment? EJNMMI Res. 2017 Dec;7(1):48. doi: 10.1186/s13550-017-0295-y. Epub 2017 May 30. PubMed PMID: 28560582.
Rachinger W, Goetz C, Pöpperl G, Gildehaus FJ, Kreth FW, Holtmannspötter M, Herms J, Koch W, Tatsch K, Tonn JC. Positron emission tomography with O-(2-[18F]fluoroethyl)-l-tyrosine versus magnetic resonance imaging in the diagnosis of recurrent gliomas. Neurosurgery. 2005 Sep;57(3):505-11; discussion 505-11. PubMed PMID: 16145529.
Pöpperl G, Götz C, Rachinger W, Gildehaus FJ, Tonn JC, Tatsch K. Value of O-(2-[18F]fluoroethyl)- L-tyrosine PET for the diagnosis of recurrent glioma. Eur J Nucl Med Mol Imaging. 2004 Nov;31(11):1464-70. Epub 2004 Jul 10. PubMed PMID: 15248032.
Kunz M, Thon N, Eigenbrod S, Hartmann C, Egensperger R, Herms J, Geisler J, la Fougere C, Lutz J, Linn J, Kreth S, von Deimling A, Tonn JC, Kretzschmar HA, Pöpperl G, Kreth FW. Hot spots in dynamic (18)FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas. Neuro Oncol. 2011 Mar;13(3):307-16. doi: 10.1093/neuonc/noq196. Epub 2011 Feb 3. PubMed PMID: 21292686; PubMed Central PMCID: PMC3064604.
Thon N, Kunz M, Lemke L, Jansen NL, Eigenbrod S, Kreth S, Lutz J, Egensperger R, Giese A, Herms J, Weller M, Kretzschmar H, Tonn JC, la Fougère C, Kreth FW. Dynamic 18F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses. Int J Cancer. 2015 May 1;136(9):2132-45. doi: 10.1002/ijc.29259. Epub 2014 Nov 3. PubMed PMID: 25311315.
Ewelt C, Floeth FW, Felsberg J, Steiger HJ, Sabel M, Langen KJ, Stoffels G, Stummer W. Finding the anaplastic focus in diffuse gliomas: the value of Gd-DTPA enhanced MRI, FET-PET, and intraoperative, ALA-derived tissue fluorescence. Clin Neurol Neurosurg. 2011 Sep;113(7):541-7. doi: 10.1016/j.clineuro.2011.03.008. Epub 2011 Apr 20. PubMed PMID: 21507562.
Jaber M, Wölfer J, Ewelt C, Holling M, Hasselblatt M, Niederstadt T, Zoubi T, Weckesser M, Stummer W. The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors. Neurosurgery. 2016 Mar;78(3):401-11. doi: 10.1227/NEU.0000000000001020. PubMed PMID: 26366972; PubMed Central PMCID: PMC4747980.
Ibbett I, Schembri G, Cook R, Parkinson J. The role of (18)F-fluoro-ethyl-tyrosine (FET) PET in the investigation and management of suspected gliomas. World Neurosurg. 2018 Oct 6. pii: S1878-8750(18)32249-6. doi: 10.1016/j.wneu.2018.09.194. [Epub ahead of print] PubMed PMID: 30300714.
Schebesch KM, Brawanski A, Doenitz C, Rosengarth K, Proescholdt M, Riemenschneider MJ, Grosse J, Hellwig D, Höhne J. Fluorescence-guidance in non-Gadolinium enhancing, but FET-PET positive gliomas. Clin Neurol Neurosurg. 2018 Jul 19;172:177-182. doi: 10.1016/j.clineuro.2018.07.011. [Epub ahead of print] PubMed PMID: 30032095.
Buchmann N, Kläsner B, Gempt J, Bauer JS, Pyka T, Delbridge C, Meyer B, Krause BJ, Ringel F. (18)F-Fluoroethyl-l-Thyrosine Positron Emission Tomography to Delineate Tumor Residuals After Glioblastoma Resection: A Comparison with Standard Postoperative Magnetic Resonance Imaging. World Neurosurg. 2016 May;89:420-6. doi: 10.1016/j.wneu.2016.02.032. Epub 2016 Feb 15. PubMed PMID: 26893043.
  • 18f_fet_pet.txt
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