背景:可以使用PET和14-(R,S)-[18F]氟-6-硫-十七烷酸([18F]FTHA)。然而,相对较快的[18F]FTHA代谢速率显着影响组织摄取的动力学模型。因此,需要精确的色谱方法来分析未代谢的[18F]FTHA(母体级分)。在这里,我们提出了一种新的放射性代谢物分析(RMA)方法,与以前的父级分析方法相比,及其在禁食和餐后条件下的重检临床研究中的用途。我们开发了一种新的薄层色谱(TLC)RMA方法,用于分析血浆中的[18F]FTHA母体级分及其放射性代谢物,通过测试固定相和洗脱液组合。接下来,我们分析了[18F]FTHA,它的放射性代谢物,和参与临床研究的受试者的血浆放射性。共有17名肥胖或超重的参与者在禁食下两次服用[18F]FTHA,在餐后条件下两次,在注射后14分钟(第一个样品的平均值)和72分钟(最后一个样品的平均值)之间获得血浆样品。使用两种方法分析了70个血浆样品的等分试样,实现头对头的比较。我们对母体分数和血浆放射性进行了测试-重测和分组比较。
结果:新的TLC方法分离出七个[18F]FTHA放射性代谢物峰,而前面的方法分开了三个。新方法揭示了至少一种以前无法与[18F]FTHA分离的放射性代谢物。从血浆样本中,新方法的平均母分数值平均低7.2个百分点,与以前的方法相比。重复[18F]FTHA对同一主题的调查显示,可重复的血浆SUV和母体部分,在禁食和餐后条件之间具有不同的动力学。
结论:新开发的用于[18F]FTHARMA的改进的放射性TLC方法可实现准确的母体部分校正,这是获得建模[18F]FTHAPET数据的定量数据所必需的。我们对禁食和餐后条件的测试重测研究显示出强大的可重复性,并揭示了不同研究环境下[18F]FTHA代谢率的明显差异。
背景:EudraCTNo:2020-005211-48,04Feb2021;和临床试验注册表NCT05132335,29Oct2021,URL:https://classic。
结果:gov/ct2/show/NCT05132335。
BACKGROUND: Fatty acid uptake can be measured using PET and 14-(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA). However, the relatively rapid rate of [18F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [18F]FTHA (parent fraction). Here we present a new radiometabolite analysis (RMA) method, with comparison to a previous method for parent fraction analysis, and its use in a test-retest clinical study under fasting and postprandial conditions. We developed a new thin-layer chromatography (TLC) RMA method for analysis of [18F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [18F]FTHA, its radiometabolites, and plasma radioactivity from subjects participating in a clinical study. A total of 17 obese or overweight participants were dosed with [18F]FTHA twice under fasting, and twice under postprandial conditions and plasma samples were obtained between 14 min (mean of first sample) and 72 min (mean of last sample) post-injection. Aliquots of 70 plasma samples were analyzed using both methods, enabling head-to-head comparisons. We performed test-retest and group comparisons of the parent fraction and plasma radioactivity.
RESULTS: The new TLC method separated seven [18F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [18F]FTHA. From the plasma samples, the mean parent fraction value was on average 7.2 percentage points lower with the new method, compared to the previous method. Repeated [18F]FTHA investigations on the same subject revealed reproducible plasma SUV and parent fractions, with different kinetics between the fasted and postprandial conditions.
CONCLUSIONS: The newly developed improved radio-TLC method for [18F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [18F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [18F]FTHA metabolic rate under different study settings.
BACKGROUND: EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic.
RESULTS: gov/ct2/show/NCT05132335 .