An intra-individual comparison of MRI, [18F]-FET and [18F]-FLT PET in patients with high-grade gliomas.

Martha Nowosielski,Markus Hutterer,Günther Stockhammer,Andreas H Jacobs,Matthew D Difranco,Wolfgang Recheis,Marcel Seiz,Daniel Putzer,Alexander Annala

doi:10.1371/journal.pone.0095830

Abstract

ObjectivesIntra-individual spatial overlap analysis of tumor volumes assessed by MRI, the amino acid PET tracer [18F]-FET and the nucleoside PET tracer [18F]-FLT in high-grade gliomas (HGG).MethodsMRI, [18F]-FET and [18F]-FLT PET data sets were retrospectively analyzed in 23 HGG patients. Morphologic tumor volumes on MRI (post-contrast T1 (cT1) and T2 images) were calculated using a semi-automatic image segmentation method. Metabolic tumor volumes for [18F]-FET and [18F]-FLT PETs were determined by image segmentation using a threshold-based volume of interest analysis. After co-registration with MRI the morphologic and metabolic tumor volumes were compared on an intra-individual basis in order to estimate spatial overlaps using the Spearman's rank correlation coefficient and the Mann-Whitney U test.Results[18F]-FLT uptake was negative in tumors with no or only moderate contrast enhancement on MRI, detecting only 21 of 23 (91%) HGG. In addition, [18F]-FLT uptake was mainly restricted to cT1 tumor areas on MRI and [18F]-FLT volumes strongly correlated with cT1 volumes (r = 0.841, p<0.001). In contrast, [18F]-FET PET detected 22 of 23 (96%) HGG. [18F]-FET uptake beyond areas of cT1 was found in 61% of cases and [18F]-FET volumes showed only a moderate correlation with cT1 volumes (r = 0.573, p<0.001). Metabolic tumor volumes beyond cT1 tumor areas were significantly larger for [18F]-FET compared to [18F]-FLT tracer uptake (8.3 vs. 2.7 cm3, p<0.001).ConclusionIn HGG [18F]-FET but not [18F]-FLT PET was able to detect metabolic active tumor tissue beyond contrast enhancing tumor on MRI. In contrast to [18F]-FET, blood-brain barrier breakdown seems to be a prerequisite for [18F]-FLT tracer uptake.

Highlights

Magnetic resonance imaging (MRI), as the gold standard diagnostic tool for brain tumors, offers high spatial resolution and is widely available [1]
O-(2-[18F]-fluoro-Ethyl)-L-tyrosine ([18F]-FET) is an amino acid tracer frequently used in the management of glial brain tumors [8]. [18F]-FET uptake correlates with tumor cell density and proliferation rate as well as with microvascular density
FET compared to [18F]-FLT PET. [18F]-FLT was able to detect 21 of 23 high-grade gliomas (HGG) (91%) and tracer uptake was negative in tumors with no or moderate contrast enhancement (n = 2), including a glioblastoma multiforme WHO IV (GBM) IV and an AA III (Figure 1)

Summary

Introduction

Magnetic resonance imaging (MRI), as the gold standard diagnostic tool for brain tumors, offers high spatial resolution and is widely available [1]. In high-grade gliomas (HGG) the area of contrast enhancement on MRI T1-weighted sequences is generally assumed to reflect the main tumor burden [1]. Molecular imaging studies using the amino acid tracers [11C]-MET and [18F]-FET revealed that in HGG patients the ‘‘metabolic tumor volumes’’ are frequently larger on PET compared to the corresponding ‘‘morphologic contrast enhancing tumor volumes’’ on MRI. This observation indicates that the main tumor burden may be substantially underestimated on standard MRI [6,7]. For treatment monitoring [18F]-FET PET enabled earlier detection of tumor progression after concomitant chemo-/radiotherapy [15], during adjuvant chemotherapy [16,17], and in the course of anti-angiogenic therapy [18] and local treatment strategies [19,20]

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