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Quantitation of benzodiazepine receptors in human brain using the partial saturation method.

UNLABELLED
The in vivo quantification of the benzodiazepine receptor concentration in humans using PET and flumazenil (FMZ) is usually based on Scatchard analysis when the goal is to avoid blood sampling. The experimental protocols, however, include several (at least two) experiments with various specific activities in the same subject to obtain a range of bound ligand concentrations.


METHODS
We propose the partial saturation method, which is based on a natural decrease in bound ligand concentration after an FMZ injection with an average dose between a tracer dose and a saturation dose. An adequate range of bound ligand concentrations can thus be obtained from a single experiment. The free ligand concentration is estimated from the PET measurement in the pons after correction for the effect of the small receptor site concentration in this reference region.


RESULTS
The receptor concentration and affinity estimates obtained with this approach in six regions of interest agree with previously published values obtained by using more complex approaches. Receptor concentration appears to be insensitive to the uncertainties with regard to the receptor site concentration in the pons.


CONCLUSION
The partial saturation protocol can be used to estimate both the benzodiazepine receptor concentration and the FMZ affinity in routine examinations in adults (or even in children) using a single 40-min experiment without blood sampling.