Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F]fluoroethyl)-L-tyrosine PET

Purpose The follow-up of glioblastoma patients after radiochemotherapy with conventional MRI can be difficult since reactive alterations to the blood-brain barrier with contrast enhancement may mimic tumour progression (i.e. pseudoprogression, PsP). The aim of this study was to assess the clinical value of O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) PET in the differentiation of PsP and early tumour progression (EP) after radiochemotherapy of glioblastoma. Methods A group of 22 glioblastoma patients with new contrast-enhancing lesions or lesions showing increased enhancement (>25%) on standardMRI within the first 12 weeks after completion of radiochemotherapy with concomitant temozolomide (median 7 weeks) were additionally examined using amino acid PET with F-18-FET. Maximum and mean tumour-to-brain ratios (TBRmax, TBRmean) were determined. F-18-FET uptake kinetic parameters (i.e. patterns of time-activity curves, TAC) were also evaluated. Classification as PsP or EP was based on the clinical course (no treatment change at least for 6 months), follow-up MR imaging and/or histopathological findings. Imaging results were also related to overall survival (OS). Results PsP was confirmed in 11 of the 22 patients. In patients with PsP, F-18-FET uptake was significantly lower than in patients with EP (TBRmax 1.9 +/- 0.4 vs. 2.8 +/- 0.5, TBRmean 1.8 +/- 0.2 vs. 2.3 +/- 0.3; both P<0.001) and presence of MGMT promoter methylation was significantly more frequent (P=0.05). Furthermore, a TAC type II or III was more frequently present in patients with EP (P=0.04). Receiver operating characteristic analysis showed that the optimal F-18-FET TBRmax cut-off value for identifying PsP was 2.3 (sensitivity 100 %, specificity 91 %, accuracy 96 %, AUC 0.94 +/- 0.06; P<0.001). Univariate survival analysis showed that a TBRmax <2.3 predicted a significantly longer OS (median OS 23 vs. 12 months; P=0.046). Conclusion F-18-FET PET may facilitate the diagnosis of PsP following radiochemotherapy of glioblastoma.