Doze P, Van Waarde A, Elsinga P H, Van-Loenen Weemaes A M, Willemsen A T, Vaalburg W
PET Center, Groningen University Hospital, The Netherlands.
Eur J Pharmacol. 1998 Jul 24;353(2-3):215-26. doi: 10.1016/s0014-2999(98)00418-x.
S-1'-[18F]fluorocarazolol (S-(-)-4-(2-hydroxy-3-(1'-[18F]fluoroisopropyl)-aminopropoxy)carba zole, a non-subtype-selective beta-adrenoceptor antagonist) has been investigated for in vivo studies of beta-adrenoceptors. Previous results indicated that uptake of this radioligand in heart and lung can be inhibited by beta-adrenoceptor agonists and antagonists. In the present study, blocking, displacement and saturation experiments were performed in rats, in combination with metabolite analysis to investigate the suitability of this radioligand for in vivo positron emission tomography (PET) imaging and quantification of beta-adrenoceptors in the brain. The results demonstrate that, (i) the uptake of S-1'-[18F]fluorocarazolol reflects specific binding to beta-adrenoceptors, (ii) binding of S-1'-[18F]fluorocarazolol to atypical or non-beta-adrenergic sites is negligible, (iii) uptake of radioactive metabolites in the brain is less than 25% of total radioactivity, 60 min after injection, (iv) in vivo measurements of receptor densities (Bmax) in cortex, cerebellum, heart, lung and erythrocytes are within range of densities determined from in vitro assays, (v) binding of S-1'-[18F]fluorocarazolol can be displaced. In conclusion, S-1'-[18F]fluorocarazolol seems to possess the appropriate characteristics to visualize and quantify beta-adrenoceptors in vivo in the central nervous system using PET.
S-1'-[¹⁸F]氟卡拉洛尔（S-(-)-4-(2-羟基-3-(1'-[¹⁸F]氟异丙基)-氨基丙氧基)咔唑，一种非亚型选择性β-肾上腺素能受体拮抗剂）已被用于β-肾上腺素能受体的体内研究。先前的结果表明，这种放射性配体在心脏和肺中的摄取可被β-肾上腺素能受体激动剂和拮抗剂抑制。在本研究中，对大鼠进行了阻断、置换和饱和实验，并结合代谢物分析，以研究这种放射性配体用于体内正电子发射断层扫描（PET）成像和定量大脑中β-肾上腺素能受体的适用性。结果表明，(i) S-1'-[¹⁸F]氟卡拉洛尔的摄取反映了与β-肾上腺素能受体的特异性结合，(ii) S-1'-[¹⁸F]氟卡拉洛尔与非典型或非β-肾上腺素能位点的结合可忽略不计，(iii) 注射后60分钟，大脑中放射性代谢物的摄取量小于总放射性的25%，(iv) 皮层、小脑、心脏、肺和红细胞中受体密度（Bmax）的体内测量值在体外测定的密度范围内，(v) S-1'-[¹⁸F]氟卡拉洛尔的结合可被置换。总之，S-1'-[¹⁸F]氟卡拉洛尔似乎具有合适的特性，可利用PET在体内可视化和定量中枢神经系统中的β-肾上腺素能受体。
