title: A simplified method for the measurement of nonmetabolized 2-[18F]F-A-85380 in blood plasma using solid-phase extraction.
abstract: 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.
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, DHHS, Baltimore, MD 21224, USA.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Shumway
authors.forename: Olga A
authors.initials: OA
authors.lastname: Pavlova
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Mukhin
mesh_terms: D000818:Animals; D001384:Azetidines / Q000097:blood*; D001774:Blood Chemical Analysis / Q000379:methods*; D000882:Haplorhini; D006801:Humans; D011725:Pyridines / Q000097:blood*; D019275:Radiopharmaceuticals / Q000097:blood; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods*
chemical_list: C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D019275:Radiopharmaceuticals