O-(2-[F-18]fluoroethyl)-L-tyrosine uptake and blood-brain barrier permeability under anti-angiogenic therapy in rat glioma models

350 Objectives Positron emission tomography (PET) with O-(2-[F-18]fluoroethyl) -L- tyrosine (FET) is used for therapy monitoring of brain tumors. Under anti-angiogenic therapy with bevacizumab, MRI often shows a reduction of contrast enhancement despite tumor progression (so-called pseudo-regression). This study examines the tumoral FET uptake under anti-angiogenic therapy in relation to the permeability of the blood-brain barrier (BBB). Methods Human U87 glioma cells were implanted into the striatum of 25 immunodeficient RNU rats. After 13-14 days of tumor growth, a dynamic FET PET (60 min) was performed followed by preparation of brains. Group 1 (n=9) received a short-term therapy with 45 mg/kg i.v. bevacizumab 48 h prior to PET scan. Group 2 (n=10) received a long-term therapy with 10 mg/kg i.v. bevacizumab 9 days and 48 hours before FET PET. The BBB permeability was histologically determined based on the extravasation of Evans Blue (2% Evans Blue i.v. 30 min before sacrifice). As a control group, FET PET scans of the short-term group before start of the treatment (n=7) were evaluated as well as Evans Blue extravasation of 6 untreated animals. The FET uptake was measured by volume of-interest (VOI) analysis (kinetics, SUV, tumor/brain ratio). Results The BBB permeability slightly decreased under bevacizumab therapy in the short-term group, while the decrease was significant in the long-term group compared to the control group (P=0.014). The FET accumulation kinetics in all three groups showed a plateau-like form and were congruent after 20 min p.i.. Under bevacizumab therapy, tumor SUV and tumor/brain ratio showed no significant differences compared to the control Group. Conclusions Under anti-angiogenic therapy with bevacizumab, the observed changes in BBB permeability showed no significant impact on the FET uptake of brain tumors. These studies confirm that the FET PET is superior to MRI during treatment monitoring of brain tumors under anti-angiogenic therapy.