Kinetic modeling of 52Fe/52mMn-citrate at the blood-brain barrier by positron emission tomography

Abstract

The kinetics of iron at the blood-brain barrier of the monkey were studied in vivo using positron emission tomography (PET) and the tracer 52Fe/52mMn-citrate. 52mMn is the β+-emitting daughter nuclide of 52Fe and therefore contributes to the observed signal and background in the PET images and may influence the quantification of physiological relevant iron parameters. The kinetics of pure 52mMn-citrate at the blood-brain barrier of the monkey were studied experimentally, and the analysis of the data with a reasonable compartment model led to equal efflux and influx parameters for Mn (1.35 ± 0.3 x 10-2 min-1). By using complexes between Mn and diethylenetriaminepentaacetic acid, the validity of the proposed model could be confirmed. To describe the observed kinetics of 52Fe/52mMn- citrate, the manganese model was coupled to an iron model, which finally allowed the quantification of two iron-specific parameters: an input rate into global brain tissue of 7.15 ± 2.6 x 10-4 min-1 and a time delay of roughly 24 min to account for the observed activities. The simpler linearization procedure has been proposed and could be applied to all our data sets and is able to replace the complicated nonlinear iron/manganese tracer kinetic model neglecting any influence of manganese on the analysis.