Comparison of C-14-sucrose delivery to the brain by intravenous, intraventricular, and convection-enhanced intracerebral infusion

Object. The authors evaluated convection-enhanced delivery (CED) of C-14-su crose to the rat brain as a method of enhancing cerebral drug delivery and compared it with intravenous (IV) and intraventricular (IVT) routes of admi nistration. Methods. Groups of rats received C-14-sucrose by bolus IV infusion, IVT inf usion for 1, 2, or 7 days at 0.17 mu l/minute, or CED at rates from 0.01 to 0.5 mu l/minute for periods from 1 hour to 7 days. Radioisotope distributi on and concentration in tissue were analyzed using quantitative autoradiogr aphy. Intravenously administered sucrose reached the entire brain, but leve ls in tissue were low. After IVT administration, sucrose levels in tissue w ere high at, and declined exponentially away from, the ventricular surface. Chronic CED administration maintained high levels of sucrose in tissue tha t focally were up to 10,000 times higher than in the TV group. The isotope distribution pattern after chronic CED infusions indicated a central compon ent that resulted from convention and a peripheral component in gray matter that was the result of diffusion. The brain influx (0.42 mu l/g/min) and d iffusion constants of sucrose (2.8 x 10(-6) cm(2)/second) were similar to r eported values. The total brain afflux constant was 0.0044 minute, whereas the blood-brain barrier (BBB) efflux constant was 0.0016 minute. There were no pathological changes in the brains after CED except those associated wi th cannula insertion. Sucrose, which was thought to be inert, was found to interact with brain tissue; up to 25% was bound to an unidentified tissue c omponent. Conclusions. Chronic CED appears to be a potentially useful method for sign ificantly circumventing the BBB and increasing delivery of water-soluble dr ugs to the brain.