Parametric images of the extrastriatal D2 receptor density obtained using a high-affinity ligand (FLB 457) and a double-saturation method

Citation
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
Citations number
22
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
ISSN journal
0271678X → ACNP
Volume
21
Issue
12
Year of publication
2001
Pages
1493 - 1503
Database
ISI
SICI code
0271-678X(200112)21:12<1493:PIOTED>2.0.ZU;2-T
Abstract
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).