J. Delforge et al., Parametric images of the extrastriatal D2 receptor density obtained using a high-affinity ligand (FLB 457) and a double-saturation method, J CEREBR B, 21(12), 2001, pp. 1493-1503
The potential of positron emission tomography for the quantitative estimati
on of receptor concentration in extrastriatal regions has been limited in t
he past because of the low density of the D2 receptor sites in these region
s and the insufficient affinity of the most widely used radioligands for do
pamine receptors. The new method described in this paper permits the estima
te of the D2 receptor concentration in the extrastriatal regions using a tw
o-injection protocol and FLB 457, a ligand with a high affinity (20 pmol/L
in vitro) with D2 dopamine receptors. This approach is not valid for the st
riatal regions because some hypotheses cannot be verified (because of the h
igh receptor concentration in these regions). The experimental protocol inc
ludes two injections with ligand doses designed to significantly occupy the
extrastriatal receptor sites (approximate to 90%), while leaving less than
60% of the receptor sites occupied by the ligand in the striatal regions.
The results obtained using this double-saturation method are in line with t
he concentration estimates previously obtained using the multiinjection app
roach. The receptor concentration is 2.9 +/- 0.5 pmol/mL in the thalamus, 1
.0 +/- 0.2 pmol/mL in the temporal cortex, and 0.35 +/- 0.13 pmol/mL in the
occipital cortex. This study provides new arguments supporting the presenc
e of a small receptor-site concentration in the cerebellum, estimated at 0.
35 +/- 0.16 pmol/mL The simplicity of the calculation used to estimate the
receptor concentration lends itself easily to parametric imaging. The recep
tor concentration is estimated pixel by pixel, without filtering. This meth
od permits estimation of the extrastriatal D2 receptor concentration using
an experimental protocol that can easily be used in patient studies (ie., s
ingle experiment, no blood sampling, short experiment duration).