PURPOSE: Our goal was to use positron emission tomography (PET) to analyze the movement of radiolabeled agents in tissue to enable direct measurement of drug delivery to the brain. PROCEDURES: Various (11)C- and (18) F-labeled compounds were delivered directly to an agarose phantom or rat striatum. Concentration profiles were extracted for analysis and fitted to diffusion models. RESULTS: Diffusion coefficients ranged from 0.075 ± 0.0026 mm(2)/min ([(18) F]fluoride ion, 18 Da) to 0.0016 ± 0.0018 mm(2)/min ([(18) F]NPB4-avidin, 68 kDa) and matched well with predictions based on molecular weight (R (2) = 0.965). The tortuosity of the brain extracellular space was estimated to be 1.56, with the tissue clearance halftime of each tracer in the brain varying from 19 to 41 min. CONCLUSIONS: PET is an effective modality to directly quantify the movement of locally delivered drugs or drug carriers. This continuous, noninvasive assessment of delivery will aid the design of better drug delivery methods.
PURPOSE: Our goal was to use positron emission tomography (PET) to analyze the movement of radiolabeled agents in tissue to enable direct measurement of drug delivery to the brain. PROCEDURES: Various (11)C- and (18) F-labeled compounds were delivered directly to an agarose phantom or rat striatum. Concentration profiles were extracted for analysis and fitted to diffusion models. RESULTS: Diffusion coefficients ranged from 0.075 ± 0.0026 mm(2)/min ([(18) F]fluoride ion, 18 Da) to 0.0016 ± 0.0018 mm(2)/min ([(18) F]NPB4-avidin, 68 kDa) and matched well with predictions based on molecular weight (R (2) = 0.965). The tortuosity of the brain extracellular space was estimated to be 1.56, with the tissue clearance halftime of each tracer in the brain varying from 19 to 41 min. CONCLUSIONS: PET is an effective modality to directly quantify the movement of locally delivered drugs or drug carriers. This continuous, noninvasive assessment of delivery will aid the design of better drug delivery methods.
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