that very critically discusses the characteristics of 18 F-GE180 as a PET tracer for the 18-kDa mitochondrial translocator protein (TSPO) in human brain.This follows a previously published and rather similar letter and thus offers little information that is substantially new [2].The main hypotheses of are still that F-GE180 is driven by the BBB disruption only.The authors appear to have disregarded this argument in their current letter [1].The discrepancy between gadolinium N. L.
PURPOSE: Gliomas with an isocitarate dehydrogenase (IDH) wildtype (wt) status have a dismal prognosis comparable to glioblastoma as reflected by the 2016 WHO classification of gliomas. In order to ensure timely adjustment of surgical and adjuvant treatment strategy, demand for non-invasive imaging methods is high. 18F-FET-PET has been shown to be an important diagnostic tool for glioma management, delivering information on prognosis and therapy response. Aim of this study was to evaluate dynamic 18F-FET-PET for non-invasive evaluation of IDH wt status prior to therapy. 341 patients with WHO II-IV glioma were included, in whom IDH mutation status, MRI and dynamic 18F-FET-PET scans were available at initial diagnosis. We assessed sensitivity, specificity, accuracy and positive as well as negative predictive values for maximal tumour-to-background ratio (TBRmax) and minimal time-to-peak (TTPmin) for prediction of IDH wt status in the entire group as well as in the subgroup of non-contrast enhancing (non-CE) tumors. Molecular analyses revealed 178 IDH mutant and 163 IDH wt tumors; 270 patients were classified as FET-positive, in these cases, TTP analysis was performed. Median TBRmax in IDH wt gliomas was 3.1 compared to 2.8 in IDH mutant tumors (p=<0.01). ROC-analyses revealed no reliable cut-off using TBRmax, due to high overlap of the two groups. In contrast, searching for a threshold in dynamic analysis, TTPmin 12.5 minutes identified IDH wt gliomas with a high positive predictive value (accuracy: 79%, PPV: 87%; NPV: 72%). In the subgroup of non-CE glioma in MRI (n=161), IDH wt genotype was identified with an accuracy of 84% (PPV: 83%, NPV: 84 %). Dynamic 18F-FET PET using TTPmin analysis provides a reliable non-invasive method for detection of IDH wt genotype especially in tumors without CE on MRI and can help to identify high-risk patients prior to treatment initiation.
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A 43-year-old woman with suspected recurrence of atypical meningioma World Health Organization grade II presented extensive intracranial lesions with high Ga-DOTATATE uptake. Moreover, numerous Ga-DOTATATE-positive bone, lung, and liver lesions were seen. For final diagnosis, biopsies taken from a lung lesion revealed distant metastases of the atypical meningioma. This case underlines the high diagnostic power of Ga-DOTATATE PET/CT for the staging of meningioma even beyond cerebral or spinal lesions; in case of distant lesions in patients with known meningioma, differential diagnosis should also contain metastases despite their rare occurrence. Moreover, this case emphasizes radioligand therapy especially in metastatic meningioma.
TSPO-PET tracers are sensitive to a single-nucleotide-polymorphism (rs6971-SNP) resulting in low (LAB), medium (MAB) and high (HAB) affinity binders, but the clinical relevance for [18F]GE-180 is still unclear. We evaluate the impact of rs6971-SNP on in vivo [18F]GE-180 binding in healthy brain and in pseudo-reference tissue in neurooncological and neurodegenerative diseases. Standardized uptake values (SUV) of [18F]GE-180-PET were assessed using a manually drawn region of interest in the fronto-parietal and cerebellar hemisphere. SUVs were compared between LAB, MAB and HAB in controls, glioma, 4-repeat tauopathies (4RT) and Alzheimer’s disease (AD) subjects. Second, SUVs were compared between patients and controls within their rs6971-subgroup. After exclusion of patients with prior therapy, n=24 LABs (n=7 controls, n=5 glioma, n=6 4RT, n=6 AD) were analysed. Age- and sex-matched MABs (n=38) and HABs (n=50) were selected. LABs had lower fronto-parietal and cerebellar SUVs when compared to MABs and HABs, but no significant difference was observed between MABs and HABs. Within each rs6971 group no SUV difference between patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [18F]GE-180 quantification, revealing lower binding in LABs when compared to MABs/HABs. Fronto-parietal and cerebellar ROIs were successfully validated as pseudo-reference regions.
68Ga-DOTATATE PET/CT enables detection of meningioma tissue based on somatostatin receptor 2 expression. Transosseous extension of intracranial meningiomas is known to be an important risk factor for tumor recurrence and patient mortality. We analyzed the diagnostic performance of 68Ga-DOTATATE PET/CT and contrast-enhanced MRI (CE-MRI) for the detection of osseous infiltration using qualitative and quantitative imaging parameters. Methods: In this institutional review board-approved retrospective study, subjects were selected from 327 consecutive 68Ga-DOTATATE PET/CT examinations for evaluation of confirmed or suspected meningioma. Inclusion criteria were CE-MRI within 30 d and pathology-confirmed meningioma diagnosis with inclusion or exclusion of transosseous extension as the standard of reference. Imaging was analyzed by two readers. Tracer uptake values and meningioma volumes were determined. χ2, Mann-Whitney U, Wilcoxon signed rank, and McNemar tests, as well as receiver-operating-characteristic analyses, were performed to compare variables and diagnostic performance. Results: Eighty-two patients fulfilled the inclusion criteria. Patients with transosseous extension of meningioma (n = 67) showed significantly larger lesions (median, 12.8 vs. 3.3 mL; P < 0.001) and significantly higher tracer uptake values (median SUVmax, 14.2 vs. 7.6; P = 0.011) than patients with extraosseous meningiomas (n = 15). 68Ga-DOTATATE PET/CT in comparison to CE-MRI performed at a higher sensitivity (98.5% vs. 53.7%) while maintaining high specificity (86.7% vs. 93.3%) in the detection of osseous involvement (P < 0.001). In receiver-operating-characteristic analysis, PET/CT assessment performed better than CE-MRI (area under the curve, 0.932 vs. 0.773). PET/CT- and CE-MRI-based volume estimation yielded comparable results for extraosseous meningiomas (P = 0.132) and the extraosseous part of transosseous meningiomas (P = 0.636), whereas the volume of the intraosseous part was assessed as significantly larger by PET/CT (P < 0.001). Conclusion:68Ga-DOTATATE PET/CT enables improved detection of the transosseous extension of intracranial meningiomas compared with CE-MRI.
The 18kDa translocator protein (TSPO) is overexpressed in brain tumours. 18F-GE-180, a novel TSPO-ligand, has shown a high target-to-background contrast in glioblastoma. However, the association with the tumoral histology and molecular genetic features is still unknown. Therefore, we correlated uptake characteristics in 18F-GE-180 PET with the individual histological tumour grade and molecular genetic features.
Abstract A 25-year-old man presented with headache and intracranial pressure symptoms. On MRI, an intracranial lesion was detected in the right thalamus with exophytic growth into the third ventricle and inhomogeneous contrast enhancement without necrosis. Dual amino acid ( 18 F-FET) and TSPO ( 18 F-GE-180) PET imaging showed high tumor-to-background ratios in both scans and a short time-to-peak in 18 F-FET uptake dynamics. Biopsy revealed a diffuse midline glioma, H3K27M-mutant (WHO grade IV), a novel entity in the 2016 WHO classification with poor clinical outcome. Our case shows that the highly aggressive features of this tumor entity can be visualized in vivo by both PET modalities.
