Delforge J, Bottlaender M, Loc'h C, Dolle F, Syrota A
Service Hospitalier Frédéric Joliot, Commissariat à l'Energie Atomique, CEA/DSV, Orsay, France.
J Cereb Blood Flow Metab. 2001 Dec;21(12):1493-503. doi: 10.1097/00004647-200112000-00014.
The potential of positron emission tomography for the quantitative estimation of receptor concentration in extrastriatal regions has been limited in the past because of the low density of the D2 receptor sites in these regions and the insufficient affinity of the most widely used radioligands for dopamine receptors. The new method described in this paper permits the estimate of the D2 receptor concentration in the extrastriatal regions using a two-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 striatal regions because some hypotheses cannot be verified (because of the high receptor concentration in these regions). The experimental protocol includes two injections with ligand doses designed to significantly occupy the extrastriatal receptor sites (approximately 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 the concentration estimates previously obtained using the multiinjection approach. 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 presence 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 receptor concentration is estimated pixel by pixel, without filtering. This method permits estimation of the extrastriatal D2 receptor concentration using an experimental protocol that can easily be used in patient studies (i.e., single experiment, no blood sampling, short experiment duration).
过去，由于纹状体以外区域的D2受体位点密度较低，且最常用的放射性配体对多巴胺受体的亲和力不足，正电子发射断层扫描在定量估计这些区域受体浓度方面的潜力受到限制。本文所述的新方法允许使用双注射方案和FLB 457（一种与D2多巴胺受体具有高亲和力的配体，体外亲和力为20 pmol/L）来估计纹状体以外区域的D2受体浓度。这种方法对纹状体区域无效，因为一些假设无法得到验证（由于这些区域的受体浓度较高）。实验方案包括两次注射，配体剂量设计为能显著占据纹状体以外的受体位点（约90%），而使纹状体区域中配体占据的受体位点少于60%。使用这种双饱和方法获得的结果与先前使用多次注射方法获得的浓度估计值一致。受体浓度在丘脑中为2.9±0.5 pmol/mL，在颞叶皮质中为1.0±0.2 pmol/mL，在枕叶皮质中为0.35±0.13 pmol/mL。这项研究提供了新的证据支持小脑存在少量受体位点浓度，估计为0.35±0.16 pmol/mL。用于估计受体浓度的计算方法简单，易于进行参数成像。逐像素估计受体浓度，无需滤波。这种方法允许使用一种实验方案来估计纹状体以外的D2受体浓度，该方案可轻松用于患者研究（即单次实验、无需采血、实验持续时间短）。
