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Noninvasive tumor growth monitoring is of particular interest for the evaluation of experimental glioma therapies. This study investigates the potential of positron emission tomography (PET) using  O -(2- 18 F-fluoroethyl)-L-tyrosine ([ 18 F]-FET) to determine tumor growth in a murine glioblastoma (GBM) model—including estimation of the biological tumor volume (BTV), which has hitherto not been investigated in the pre-clinical context. Fifteen GBM-bearing mice (GL261) and six control mice (shams) were investigated during 5 weeks by PET followed by autoradiographic and histological assessments. [ 18 F]-FET PET was quantitated by calculation of maximum and mean standardized uptake values within a universal volume-of-interest (VOI) corrected for healthy background (SUVmax/BG, SUVmean/BG). A partial volume effect correction (PVEC) was applied in comparison to  ex vivo  autoradiography. BTVs obtained by predefined thresholds for VOI definition (SUV/BG: ≥1.4; ≥1.6; ≥1.8; ≥2.0) were compared to the histologically assessed tumor volume ( n  = 8). Finally, individual “optimal” thresholds for BTV definition best reflecting the histology were determined. In GBM mice SUVmax/BG and SUVmean/BG clearly increased with time, however at high inter-animal variability. No relevant [ 18 F]-FET uptake was observed in shams. PVEC recovered signal loss of SUVmean/BG assessment in relation to autoradiography. BTV as estimated by predefined thresholds strongly differed from the histology volume. Strikingly, the individual “optimal” thresholds for BTV assessment correlated highly with SUVmax/BG (ρ = 0.97,  p  < 0.001), allowing SUVmax/BG-based calculation of individual thresholds. The method was verified by a subsequent validation study ( n  = 15, ρ = 0.88,  p  < 0.01) leading to extensively higher agreement of BTV estimations when compared to histology in contrast to predefined thresholds. [ 18 F]-FET PET with standard SUV measurements is feasible for glioma imaging in the GBM mouse model. PVEC is beneficial to improve accuracy of [ 18 F]-FET PET SUV quantification. Although SUVmax/BG and SUVmean/BG increase during the disease course, these parameters do not correlate with the respective tumor size. For the first time, we propose a histology-verified method allowing appropriate  individual  BTV estimation for volumetric  in vivo  monitoring of tumor growth with [ 18 F]-FET PET and show that standardized thresholds from routine clinical practice seem to be inappropriate for BTV estimation in the GBM mouse model.

Monitoring of Tumor Growth with [18F]-FET PET in a Mouse Model of Glioblastoma: SUV Measurements and Volumetric Approaches