[18F]2-fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Estimation of Blood-brain Barrier Permeability in vivo

Abstract

Purpose The non-transported and non-metabolized sorbitol derivative [18F]2-fluoro-2-deoxy-sorbitol ([18F]FDS) can be straightforwardly obtained from chemical reduction of commercial [18F]2-deoxy-2-fluoro-D-glucose. [18F]FDS was evaluated as a small-molecule (paracellular) marker of blood-brain barrier (BBB) integrity for PET. Methods Five mice underwent focused ultrasound (FUS) to generate spatially controlled BBB disruption in the right hemisphere. PET kinetics of [18F]FDS in each brain hemisphere were described by a 1-tissue compartment model using an image-derived input function. Results BBB disruption resulted in a 2.4±0.8-fold increase in the brain distribution (VT, p<0.01) of [18F]FDS. Enhanced brain uptake was associated with an increase in the influx transfer rate K1 (+1.4±0.7-fold, p<0.05) and a decrease in the efflux transfer rate k2 (-1.7±0.4-fold, p<0.01). Conclusion Thanks to the quantitative performance of PET compared with other neuroimaging techniques, [18F]FDS PET and kinetic modelling provides a readily available and sensitive method for non-invasive determination of different levels of BBB permeability in vivo.