van Waarde A, Visser T J, Posthumus H, Elsinga P H, Anthonio R L, van Loenen-Weemaes A M, Visser G M, Beaufort-Krol G C, Paans A M, Vaalburg W
Positron Emission Tomography (PET) Center, University Hospital, Groningen, Netherlands.
J Chromatogr B Biomed Appl. 1996 Apr 12;678(2):253-60. doi: 10.1016/0378-4347(95)00472-6.
Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H-carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2- propanol (S-1'-[18F]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma is necessary for analysis of PET images in terms of receptor densities. We have determined I and its radioactive metabolites in rat, sheep and human plasma, using (1) solid-phase extraction (C18) followed by reversed-phase HPLC and (2) direct injection of untreated plasma samples on an internal-surface reversed-phase (ISRP) column. The two methods were in good agreement. Unmodified I decreased from over 99% initially to less than 5%, 5-10% and 20% at 60 min post-injection in rats, sheep and human volunteers, respectively. Protein binding in sheep and human plasma was determined by ultrafiltration. The fraction of total plasma radioactivity bound to protein and the fraction representing unmodified radioligand were linearly correlated, suggesting that fluorocarazolol was more than 70% protein-bound, whereas its metabolites showed negligible protein binding. Direct injection of plasma on an ISRP column seems a convenient method for quantification of lipophilic radioligands such as fluorocarazolol.
心肌和肺β-肾上腺素能受体可用2-(S)-(-)-(9H-咔唑-4-基-氧基)-3-[1-(氟甲基)乙基]氨基-2-丙醇（S-1'-[¹⁸F]氟咔唑醇，I）进行成像。为了根据受体密度分析PET图像，对血浆中未修饰的氟咔唑醇进行定量是必要的。我们使用(1)固相萃取（C18），然后进行反相高效液相色谱法，以及(2)将未处理的血浆样品直接进样到内表面反相（ISRP）柱上，测定了大鼠、绵羊和人血浆中的I及其放射性代谢物。这两种方法结果吻合良好。在大鼠、绵羊和人类志愿者体内，注射后60分钟时，未修饰的I分别从最初的超过99%降至不到5%、5 - 10%和20%。通过超滤测定了绵羊和人血浆中的蛋白质结合情况。与蛋白质结合的总血浆放射性分数和代表未修饰放射性配体的分数呈线性相关，这表明氟咔唑醇与蛋白质的结合率超过70%，而其代谢物的蛋白质结合可忽略不计。将血浆直接进样到ISRP柱上似乎是一种用于定量亲脂性放射性配体如氟咔唑醇的便捷方法。
