A simplified method for the measurement of nonmetabolized 2-[18F]F-A-85380 in blood plasma using solid-phase extraction

Quantification of α4β2* nicotinic acetylcholine receptors using 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]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-[18F]FA. This method allows many samples to be processed in a short period of time. SPE effectively separated 2-[18F]FA from radioactive metabolites typically observed in blood plasma after administration of radioligand in humans. Measurements of the 2-[18F]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-[18F]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-[18F]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-[18F]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-[18F]FA concentration when measurement of individual metabolites is not required.