FET PET reveals considerable spatial differences in tumour burden compared to conventional MRI in newly diagnosed glioblastoma

Abstract

Purpose: Contrast enhancement (CE) in MRI is usually the target for resection or radiotherapy target volume definition in glioblastomas. However, the solid tumour mass may extend beyond areas of CE. Amino acid PET can detect such tumour parts that show no CE. We systematically investigated tumour volumes delineated by amino acid PET and MRI in newly diagnosed, untreated glioblastoma patients. Methods: Preoperatively, 50 patients with neuropathologically confirmed glioblastoma underwent O-(2-[ 18 F]-fluoroethyl)-L-tyrosine (FET) PET, fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced MRI. Areas of CE were manually segmented. FET PET tumour volumes were segmented using a tumour-to-brain ratio ≥1.6. The percentage of overlapping volumes (OV), Dice and Jaccard spatial similarity coefficients (DSC; JSC) were calculated. FLAIR images were evaluated visually. Results: In 86% of patients (n=43), the FET tumour volume was significantly larger than the volume of CE (21.5±14.3 mL vs. 9.4±11.3 mL; P<0.001). Forty patients (80%) showed both an increased uptake of FET and CE. In these 40 patients, the spatial similarity between FET and CE was low (mean DSC, 0.39±0.21; mean JSC, 0.26±0.16). Ten patients (20%) showed no CE, and one of these patients showed no FET uptake. In 10% of patients (n=5), increased FET uptake was present outside of areas of FLAIR hyperintensity. Conclusions: Our data show that the metabolically active tumour volume delineated by FET PET is significantly larger than tumour volume delineated by CE. Furthermore, the data strongly suggest that the information derived from both imaging modalities should be integrated into the management of newly diagnosed glioblastoma patients.

Simultaneous FET-PET and contrast-enhanced MRI based on hybrid PET/MR improves delineation of tumor spatial biodistribution in gliomas: a biopsy validation study

“…Compared with CE MRI, amino acid PET imaging, when used with tracers such as 11 C-MET [19,22] and 18 F-FET [23], often reveals a larger tumor spatial distribution in GBM patients. Among these previous studies, simultaneous PET and MRI acquisition was used with a hybrid PET/MR only in Lohnmann's study (35 of 50 patients).…”

Treatment-Related Uptake of O-(2-18F-Fluoroethyl)-l-Tyrosine and l-[Methyl-3H]-Methionine After Tumor Resection in Rat Glioma Models

“…In addition to astrogliosis, other mechanisms for increased amino acid accumulation such as disruption of the bloodbrain barrier, increased perfusion, or edema must also be discussed. In different preclinical and clinical studies (31)(32)(33)(34)(35), however, no significant influence of blood-brain barrier disruption, microvessel density, perfusion, or edema on 18 F-FET uptake has been reported. Furthermore, 18 F-FET is not involved in protein synthesis, but for 3 H-MET uptake, an influence of protein incorporation cannot be excluded.…”

Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors

“…For the planning of diagnostic and therapeutic procedures, the precise delineation of tumor spread is essential. For example, the tumor extent as assessed by amino acid PET provides valuable information for planning stereotactic biopsies, resection, and radiotherapy [1,[50][51][52]. For [ 11 C]MET and [ 18 F]FET, it has been shown that the delineation of tumor extent, particularly in non-enhancing gliomas, can be assessed with high accuracy using amino acid PET [51,53].…”

“…Preliminary data suggest that newer tracers such as [ 18 F]FACBC PET are also helpful in identifying metabolically active and non-contrast enhancing tumor regions in glioma patients [54][55][56]. Moreover, it has been shown that in the majority of cases, the metabolically active tumor burden as assessed by amino acid PET extends considerably beyond the volume of MRI contrast enhancement, which is of significant relevance for subsequent treatment planning [1,7,53,57]. Regarding the comparability of PET tracers for this indication, [ 11 C]MET, [ 18 F]FET, and [ 18 F]FDOPA seem to be equally informative [58][59][60][61].…”

“…For the management of patients with brain tumors, clinicians frequently need to rely on imaging information obtained from anatomical magnetic resonance imaging (MRI) before, during, and after the treatment. While contrast-enhanced MRI is of paramount value in neuro-oncology, its specificity for neoplastic tissue is low, and changes of the blood-brain barrier permeability as indicated by contrast enhancement are not limited to tumor tissue [1][2][3][4][5][6][7]. Nevertheless, precise delineation of tumor extent, including non-enhancing tumor subregions, is decisive for several diagnostic and therapeutic steps (e.g., planning of biopsy, surgery, or radiotherapy) [7,8].…”