Neuroimaging enables the noninvasive evaluation of glioma and is considered to be one of the key factors for individualized therapy and patient management, since accurate diagnosis and demarcation of viable tumor tissue is required for treatment planning as well as assessment of treatment response. Conventional imaging techniques like MRI and CT reveal morphological information but are of limited value for the assessment of more specific and reproducible information about biology and activity of the tumor. Molecular imaging with PET is increasingly implemented in neuro-oncology, since it provides additional metabolic information of the tumor, both for patient management as well as for evaluation of newly developed therapeutics. Different molecular processes have been proposed to be useful, like glucose consumption, expression of amino acid transporters, proliferation rate, membrane biosynthesis, and hypoxia. Thus, PET might help neuro-oncologists gain further insights into tumor biology by "true molecular imaging" as well as understand treatment-related phenomena. This review describes the method of PET acquisition as well as the tracers used to image biological processes in gliomas. Furthermore, it considers the clinical impact of PET on the use of currently available radiotracers, which were shown to be potentially valuable for discrimination between neoplastic and nonneoplastic tissue, as well as on tumor grading, determinination of treatment response, and providing an outlook toward further developments.

OBJECTIVE The aim of this prospective longitudinal study was to identify static and dynamic O-(2-[(18)F]fluoroethyl)-l-tyrosine PET ((18)FET-PET)-derived imaging biomarkers in patients with glioblastoma (GBM). METHODS Seventy-nine patients with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy (unresectable tumors) and 37 patients microsurgical tumor resection. All patients were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide (RCx/TMZ). (18)FET-PET evaluation using static and dynamic analysis was done before biopsy/resection, after resection, 4 to 6 weeks following RCx, and after 3 cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic factors were obtained from proportional hazards models. RESULTS Biological tumor volume before RCx (BTVpreRCx) was the most important (18)FET-PET-derived imaging biomarker and was independent of MGMT promoter methylation and clinical prognostic factors: patients with smaller BTVpreRCx had significantly longer progression-free and overall survival (OS). (18)FET time-activity curves (TACs) before treatment and their changes after RCx were also related to outcome; patients with initially increasing TACs experienced longer OS. CONCLUSION BTVpreRCx and TAC represent important (18)FET-PET-derived imaging biomarkers in GBM. Increasing TACs are associated with prolonged OS. The BTVpreRCx is a strong prognostic factor for progression-free survival and OS independent of the mode of surgery. Our data furthermore suggest that patients harboring resectable GBM might benefit from maximal PET-guided tumor resection. Originally published at: Suchorska, B; Jansen, N L; Linn, J; Kretzschmar, H; Janssen, H; Eigenbrod, S; Simon, M; Pöpperl, G; Kreth, F W; la Fougere, C; Weller, M; Tonn, J C (2015). Biological tumor volume in 18FET-PET before radiochemotherapy correlates with survival in GBM. Neurology, 84 (7)

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Despite advances in diagnosis and the use of different therapeutic regimens in astrocytic high-grade glioma (HGG), the prognosis for patients remains grim. Additional pretherapeutic information is needed to tailor management. To gain additional prognostic information at primary diagnosis, we investigated the value ofWe retrospectively evaluated 121 patients who had a primary diagnosis of astrocytic HGG (51 World Health Organization [WHO] grade III; 70 WHO IV) and underwent dynamic 18 F-FET PET before histopathologic assessment. We assessed static parameters (maximal and mean tumoral standardized uptake value corrected for mean background activity in the contralateral hemisphere [SUV max / BG and SUV mean /BG, respectively], biologic tumor volume) and dynamic time-activity curves, including minimal time to peak (TTP min ). The prognostic influence of PET parameters and other clinical parameters on progression-free and overall survival was evaluated using uni-and multivariate Cox regression and Kaplan-Meier survival estimates. Results: In the group overall, median progression-free survival and overall survival were 12.2 and 21.9 mo. SUV max /BG, SUV mean /BG, and biologic tumor volume were significantly higher in WHO IV than in WHO III gliomas; median TTP min was 12.5 min in both groups. On univariate analysis, the factors age, WHO grade, O6-methylguanine-DNA methyltransferase promoter methylation status, contrast enhancement, initial treatment, and TTP min showed prognostic significance, with WHO grade, O6-methylguanine-DNA methyltransferase status, age, and TTP min remaining significant in the multivariate analysis. WHO grade and TTP min reached a similar fit for the prognostic evaluation. The prognosis of WHO III astrocytoma with an early TTP min of 12.5 min or less did not differ significantly from that of glioblastoma. Conclusion: Early TTP min is associated with worse outcome in patients with newly diagnosed astrocytic HGG. In the preoperative setting, TTP min can be a valuable noninvasive prognostic marker with comparable significance to WHO grade. Additionally, TTP min can help identify highly aggressive WHO III astrocytoma tumors and may help in adjusting standard treatment toward an individualized, risk-adapted therapy regime.

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Intra-tumoural PpIX concentrations exhibited pronounced inter- and intra-tumoural variations in glioblastoma, which are directly linked to variable degrees of fluorescence intensity. High intra-tumoural PpIX concentrations with strong fluorescence intensity and complete photobleaching after iPDT seem to be associated with favourable outcome. Real-time monitoring of PpIX fluorescence intensity and photobleaching turned out to be feasible and safe and might be employed for early treatment prognosis of iPDT.

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Every attempt should be undertaken to preserve language-relevant areas intraoperatively, even when they are located within the tumor. New postoperative deficits resolve in the majority of patients, which may be a result of cortical mapping as well as functional reorganization.