Noguchi Junko, Zhang Ming-Rong, Yanamoto Kazuhiko, Nakao Ryuji, Suzuki Kazutoshi
Radiochemistry Section, Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Chiba 263-8555, Japan.
Nucl Med Biol. 2008 Jan;35(1):19-27. doi: 10.1016/j.nucmedbio.2007.09.009.
The aim of this study was to characterize the in vitro binding of [(11)C]raclopride with ultrahigh specific activity (SA) in the striatum and cerebral cortex of rat brain.
[(11)C]Raclopride, a dopamine D(2) receptor ligand, with an ultrahigh SA of 4880+/-2360 GBq/micromol (132+/-64 Ci/micromol, n=25) was synthesized. In vitro binding experiment was performed using brain homogenate assay and autoradiography (ARG).
In vitro homogenate assay demonstrated that high SA [(11)C]raclopride (2520-6340 GBq/micromol; 68-171 Ci/micromol) had two-affinity (high and low) binding sites in the striatum and cerebral cortex of rat brain. In the striatum, K(d,high) and B(max,high) values were 0.005+/-0.002 nM and 0.19+/-0.04 fmol/mg tissue, respectively, while K(d,low) and B(max,low) values were 2.2+/-1.0 nM and 35.8+/-16.4 fmol/mg tissue, respectively. In the cerebral cortex, K(d,high) and B(max,high) values were 0.061+/-0.087 nM and 0.2+/-0.2 fmol/mg tissue, respectively, while K(d,low) and B(max,low) values were 2.5+/-3.2 nM and 5.5+/-4.8 fmol/mg tissue, respectively. On the other hand, only one binding site was found in the striatum and no binding site was identified in the cerebral cortex using low SA [(11)C]raclopride (44 GBq/micromol; 1.2 Ci/micromol). In vitro ARG for the rat brain using high SA [(11)C]raclopride (6212 GBq/micromol; 168 Ci/micromol) gave a coronal image of the striatum and cerebral cortex with a higher signal/noise ratio than using low SA [(11)C]raclopride (40 GBq/micromol; 1.1 Ci/micromol).
Using ultrahigh SA [(11)C]raclopride for the in vitro homogenate assay, we succeeded in detecting two-affinity binding sites of [(11)C]raclopride, not only in the striatum but also in the cerebral cortex of rat brain.
本研究旨在表征超高比活度（SA）的[(11)C]雷氯必利在大鼠脑纹状体和大脑皮质中的体外结合情况。
合成了一种多巴胺D(2)受体配体[(11)C]雷氯必利，其具有4880±2360 GBq/μmol（132±64 Ci/μmol，n = 25）的超高比活度。使用脑匀浆测定法和放射自显影术（ARG）进行体外结合实验。
体外匀浆测定表明，高比活度[(11)C]雷氯必利（2520 - 6340 GBq/μmol；68 - 171 Ci/μmol）在大鼠脑纹状体和大脑皮质中有两个亲和力（高和低）结合位点。在纹状体中，K(d,高)和B(max,高)值分别为0.005±0.002 nM和0.19±0.04 fmol/mg组织，而K(d,低)和B(max,低)值分别为2.2±1.0 nM和35.8±16.4 fmol/mg组织。在大脑皮质中，K(d,高)和B(max,高)值分别为0.061±0.087 nM和0.2±0.2 fmol/mg组织，而K(d,低)和B(max,低)值分别为2.5±3.2 nM和5.5±4.8 fmol/mg组织。另一方面，使用低比活度[(11)C]雷氯必利（44 GBq/μmol；1.2 Ci/μmol）时，在纹状体中仅发现一个结合位点，在大脑皮质中未发现结合位点。使用高比活度[(11)C]雷氯必利（6212 GBq/μmol；168 Ci/μmol）对大鼠脑进行体外ARG，得到的纹状体和大脑皮质冠状图像的信噪比高于使用低比活度[(11)C]雷氯必利（40 GBq/μmol；1.1 Ci/μmol）时。
使用超高比活度[(11)C]雷氯必利进行体外匀浆测定，我们成功检测到[(11)C]雷氯必利不仅在大鼠脑纹状体而且在大脑皮质中的两个亲和力结合位点。
