Shumway Dean A, Pavlova Olga A, Mukhin Alexey G
Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, DHHS, Baltimore, MD 21224, USA.
Nucl Med Biol. 2007 Feb;34(2):221-8. doi: 10.1016/j.nucmedbio.2006.12.001.
Quantification of alpha(4)beta(2)* nicotinic acetylcholine receptors using 2-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]FA) and positron emission tomography (PET) imaging requires measurement of nonmetabolized radioligand in blood plasma, which was previously accomplished using high-performance liquid chromatography (HPLC). Here, we introduce a one-step solid-phase extraction (SPE) method for measuring the concentration of nonmetabolized 2-[(18)F]FA. This method allows many samples to be processed in a short period of time. SPE effectively separated 2-[(18)F]FA from radioactive metabolites typically observed in blood plasma after administration of radioligand in humans. Measurements of the 2-[(18)F]FA parent fraction in healthy human volunteers obtained using the SPE method were nearly identical to those obtained using HPLC (1.3+/-5% average underestimation of SPE), and reproducibility was good within and between runs (2% and 6% coefficient of variation, respectively). SPE recovery of 2-[(18)F]FA from blood plasma was not appreciably diminished (3+/-0.6%) by a larger volume of blood plasma loaded onto the cartridge, suggesting the possibility of increasing the plasma sample volume at later times in a PET study to improve measurement sensitivity. 2-[(18)F]FA was stable in blood stored on ice over 8 h and in saline at low concentrations (<2 MBq/ml) but not at high concentrations (ca. 130 MBq/ml). Using SPE, the elimination half-life and full body distribution volume of 2-[(18)F]FA in healthy human volunteers were estimated as 4.2+/-0.8 h and 220+/-70 L, respectively. These results suggest that SPE is the method of choice for the determination of the plasma 2-[(18)F]FA concentration when measurement of individual metabolites is not required.
使用2-[(18)F]氟-3-(2(S)-氮杂环丁烷基甲氧基)吡啶(2-[(18)F]FA)和正电子发射断层扫描(PET)成像对α(4)β(2)*烟碱型乙酰胆碱受体进行定量，需要测量血浆中未代谢的放射性配体，此前这是通过高效液相色谱(HPLC)完成的。在此，我们介绍一种用于测量未代谢的2-[(18)F]FA浓度的一步固相萃取(SPE)方法。该方法能在短时间内处理多个样品。SPE有效地将2-[(18)F]FA与人类注射放射性配体后血浆中通常观察到的放射性代谢物分离。使用SPE方法获得的健康人类志愿者中2-[(18)F]FA母体分数的测量值与使用HPLC获得的测量值几乎相同(SPE平均低估1.3±5%)，并且在运行内和运行间的重现性良好(变异系数分别为2%和6%)。加载到柱上的血浆体积增加，并不会使SPE从血浆中回收2-[(18)F]FA的量明显减少(3±0.6%)，这表明在PET研究后期有可能增加血浆样品体积以提高测量灵敏度。2-[(18)F]FA在冰上储存8小时以上的血液中以及在低浓度(<2 MBq/ml)的盐水中是稳定的，但在高浓度(约130 MBq/ml)时不稳定。使用SPE，估计健康人类志愿者中2-[(18)F]FA的消除半衰期和全身分布容积分别为4.2±0.8小时和220±70升。这些结果表明，当不需要测量单个代谢物时，SPE是测定血浆中2-[(18)F]FA浓度的首选方法。
