Sorger Dietlind, Becker Georg A, Patt Marianne, Schildan Andreas, Grossmann Udo, Schliebs Reinhard, Seese Anita, Kendziorra Kai, Kluge Magnus, Brust Peter, Mukhin Alexey G, Sabri Osama
Department of Nuclear Medicine, University of Leipzig, Leipzig, 04103, Germany.
Nucl Med Biol. 2007 Apr;34(3):331-42. doi: 10.1016/j.nucmedbio.2006.12.008. Epub 2007 Feb 22.
2-[(18)F]fluoro-A-85380 (2-[(18)F]FA) is a new radioligand for noninvasive imaging of alpha4beta2* nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET) in human brain. In most cases, quantification of 2-[(18)F]FA receptor binding involves measurement of free nonmetabolized radioligand concentration in blood. This requires an efficient and reliable method to separate radioactive metabolites from the parent compound. In the present study, three analytical methods, thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and solid phase extraction (SPE) have been tested. Reversed-phase TLC of deproteinized aqueous samples of plasma provides good estimates of 2-[(18)F]FA and its metabolites. However, because of the decreased radioactivity in plasma samples, this method can be used in humans over the first 2 h after radioligand injection only. Reliable quantification of the parent radioligand and its main metabolites was obtained using reversed-phase HPLC, followed by counting of eluted fractions in a well gamma counter. Three main and five minor metabolites of 2-[(18)F]FA were detected in human blood using this method. On average, the unchanged 2-[(18)F]FA fraction in plasma of healthy volunteers measured at 14, 60, 120, 240 and 420 min after radioligand injection was 87.3+/-2.2%, 74.4+/-3%, 68.8+/-5%, 62.3+/-8% and 61.0+/-8%, respectively. In patients with neurodegenerative disorders, the values corresponding to the three last time points were significantly lower. The fraction of nonmetabolized 2-[(18)F]FA in plasma determined using SPE did not differ significantly from that obtained by HPLC (+gamma counting) (n=73, r=.95). Since SPE is less time-consuming than HPLC and provides comparable results, we conclude that SPE appears to be the most suitable method for measurement of 2-[(18)F]FA parent fraction during PET investigations.
2-[(18)F]氟-A-85380（2-[(18)F]FA）是一种新型放射性配体，用于通过正电子发射断层扫描（PET）对人脑α4β2*烟碱型乙酰胆碱受体（nAChRs）进行无创成像。在大多数情况下，2-[(18)F]FA受体结合的定量分析涉及测量血液中游离的未代谢放射性配体浓度。这需要一种高效可靠的方法来将放射性代谢物与母体化合物分离。在本研究中，测试了三种分析方法，即薄层色谱法（TLC）、高效液相色谱法（HPLC）和固相萃取法（SPE）。血浆脱蛋白水样的反相TLC能很好地估算2-[(18)F]FA及其代谢物。然而，由于血浆样品中放射性降低，该方法仅可在放射性配体注射后的前2小时内用于人体。使用反相HPLC，随后在井型γ计数器中对洗脱组分进行计数，可获得母体放射性配体及其主要代谢物的可靠定量结果。使用该方法在人体血液中检测到了2-[(18)F]FA的三种主要代谢物和五种次要代谢物。在放射性配体注射后14、60、120、240和420分钟测量时，健康志愿者血浆中未变化的2-[(18)F]FA分数平均分别为87.3±2.2%、74.4±3%、68.8±5%、62.3±8%和61.0±8%。在神经退行性疾病患者中，与最后三个时间点对应的数值显著更低。使用SPE测定的血浆中未代谢的2-[(18)F]FA分数与通过HPLC（+γ计数）获得的分数无显著差异（n = 73，r = 0.95）。由于SPE比HPLC耗时更少且结果相当，我们得出结论，在PET研究期间，SPE似乎是测量2-[(18)F]FA母体分数的最合适方法。
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