Partial saturation approach for estimating Bmax and KD
Determination of Bmax and KD is possible if PET data is collected during high and low receptor occupancy. This is usually accomplished by (at least) two radioligand injections, one with low ligand mass (high specific activity) and the other with high ligand mass (low specific activity). Delforge et al. have developed an alternative method applying single-injection protocol, where the injected radioligand dose is between a tracer dose and a saturation dose. This partial saturation approach (PSA) was shown to be suitable for producing quantitative images of receptor binding and affinity without blood sampling in [11C]flumazenil PET studies (Delforge et al., 1995, 1996, 1997).
Partial saturation method is based on the natural decrease in bound ligand concentration in the target tissue during the PET scan. The injected mass of radioligand must be sufficiently high to occupy a notable fraction of receptors, but not too high to prevent a measurable decrease in saturation level during the PET scan. Delforge et al. (1996) estimated that receptor occupancy should ideally be 60-70%, or at least 50%.
Partial saturation method may not be applicable to every PET tracer: kinetics of the binding must be sufficiently fast (high kon and koff), otherwise the decrease in occupancy would be too slow to measure reliably during the PET scan. Also, a receptor-free reference region is required.
Partial saturation approach may be especially well suited to small animal studies, where sufficiently high specific activity of the tracer may be difficult to obtain. The method has been shown to work well in mice studies with [11C]raclopride (Wimberley et al., 2014).
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Created at: 2014-09-03
Written by: Vesa Oikonen