Radiopharmacy Unit, Hospital Universitari Son Espases, Palma, Spain.
SCOPIA Research Group, Universitat de les Illes Balears, Palma, Spain.
Nucl Med Biol. 2019 Jul-Aug;74-75:34-40. doi: 10.1016/j.nucmedbio.2019.08.003. Epub 2019 Aug 20.
After its intravenous injection, [F]fluorocholine is oxidized by choline-oxidase into its main plasma metabolite, [F]fluorobetaine. If PET kinetic modeling quantification of [F]fluorocholine uptake is intended, the plasma input time-activity-curve of the parent tracer must be obtained, i.e., the fraction of the total plasma radioactivity corresponding to the nonmetabolized [F]fluorocholine at each time has to be known. Hence our aim was to develop an easy-routine Thin-Layer-Chromatography (TLC) method to separate and quantify the relative fractions of [F]fluorocholine and [F]fluorobetaine as a function of time during PET imaging in humans.
First, we tested several combinations of solvents systems and layers to select the one showing the best resolution on non-radioactive standards. Thereafter, [F]fluorobetaine was obtained through chemical oxidation of an [F]fluorocholine sample at diferent incubation times and we applied the selected TLC-system to aliquots of this oxidation solution, both in a saline and in human deproteinized plasma matrices. The plates were detected by a radio-TLC-scanner. This TLC-system was finally applied to arterial plasma samples from 9 patients with high-grade-glioma undergoing brain PET imaging and a parent fraction curve was obtained in each of them.
A TLC-system based on Silica-Gel-60//MeOH-NH was selected from the choline/betaine non-radioactive standards assay. Radiochromatograms of [F]fluorocholine oxidation solution yielded two separated and well-defined peaks, Rf = 0,03 ([F]fluorocholine) and Rf = 0.78 (F]fluorobetaine) consistent with those observed on non-radioactive standards. During the oxidation, the [F]fluorocholine radioactivity peak decreased progressively at several incubation times, while the other peak ([F]fluorobetaine) increased accordingly. The mean values of the parent fraction of [F]fluorocholine of the 9 patients studied (mean+/-SD) were 94% ± 6%, 58% ± 15%, 43% ± 10%, 39% ± 6% and 37% ± 6% at 2.8 min, 5.8 min, 8.8 min, 11.7 min and 14.7 min post-injection, respectively.
We have developed a TLC-system, easy to perform in a standard radiopharmacy unit, that enables the metabolite correction of arterial input function of [F]fluorocholine in patients undergoing PET oncologic quantitative imaging.
静脉注射[F]氟胆碱后，[F]氟胆碱被胆碱氧化酶氧化为其主要的血浆代谢物[F]氟甜菜碱。如果要对[F]氟胆碱摄取进行 PET 动力学模型定量，必须获得母体示踪剂的血浆输入时间-活性曲线，即必须知道每个时间点与未代谢的[F]氟胆碱相对应的总血浆放射性的分数。因此，我们的目的是开发一种简单的薄层色谱（TLC）方法，以在人体 PET 成像过程中分离和定量[F]氟胆碱和[F]氟甜菜碱的相对分数随时间的变化。
首先，我们测试了几种溶剂系统和层的组合，以选择在非放射性标准上显示最佳分辨率的组合。此后，通过[F]氟胆碱样品在不同孵育时间的化学氧化获得[F]氟甜菜碱，并将选定的 TLC 系统应用于该氧化溶液的等分试样中，该溶液分别在盐溶液和人去蛋白血浆基质中。使用放射性 TLC 扫描仪对平板进行检测。最后，将该 TLC 系统应用于 9 例高级别胶质瘤患者的脑 PET 成像的动脉血浆样本，并在每个样本中获得母体分数曲线。
从胆碱/甜菜碱非放射性标准测定中选择了基于硅胶 60//甲醇-NH 的 TLC 系统。[F]氟胆碱氧化溶液的放射性色谱图产生了两个分离且定义明确的峰，Rf=0.03([F]氟胆碱)和 Rf=0.78([F]氟甜菜碱)，与非放射性标准观察到的一致。在氧化过程中，[F]氟胆碱放射性峰在几个孵育时间逐渐降低，而另一个峰([F]氟甜菜碱)相应增加。9 例研究患者的[F]氟胆碱母体分数的平均值(平均值±SD)分别为 2.8 分钟、5.8 分钟、8.8 分钟、11.7 分钟和 14.7 分钟时的 94%±6%、58%±15%、43%±10%、39%±6%和 37%±6%。
我们开发了一种 TLC 系统，该系统易于在标准放射性药物单位中进行，可对接受 PET 肿瘤定量成像的患者进行[F]氟胆碱的动脉输入函数的代谢校正。
