RT Journal Article SR Electronic T1 123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1633 OP 1640 DO 10.2967/jnumed.107.042317 VO 48 IS 10 A1 Kelly P. Cosgrove A1 Effie M. Mitsis A1 Frederic Bois A1 Erin Frohlich A1 Gilles D. Tamagnan A1 Erica Krantzler A1 Edward Perry A1 Paul K. Maciejewski A1 C. Neill Epperson A1 Sharon Allen A1 Stephanie O'Malley A1 Carolyn M. Mazure A1 John P. Seibyl A1 Christopher H. van Dyck A1 Julie K. Staley YR 2007 UL http://jnm.snmjournals.org/content/48/10/1633.abstract AB The study of the effects of sex and hormones on brain chemistry and neurotransmission is of increasing importance as evidence emerges of sex differences in behavioral symptoms and treatment response in neuropsychiatric disorders. The nicotinic acetylcholine receptor (nAChR) system has been implicated in a variety of psychiatric disorders, including tobacco smoking, for which there is strong evidence supporting sex differences in behaviors and response to smoking cessation treatments. We examined the availability of nAChR containing the β2 subunit in healthy men and women and the influence of menstrual phase among women. Methods: Ten men and 19 women nonsmokers underwent one 123I-5-IA-85380 (123I-5-IA) SPECT scan and one MRI scan. A subset of 9 women, aged 18–39 y, underwent a second 123I-5-IA scan. These 9 women were scanned during the early follicular (days 4–7 in 8 subjects and day 11 in 1 subject) and mid-luteal (days 19–25) phases of their menstrual cycle. Hormone levels were measured in all women to confirm the phase of the cycle. Results: Regional brain activity (kBq/cm3) was higher (39%–54%) in women than in men nonsmokers. When regional brain activity was normalized to total plasma parent to correct for individual differences in radiotracer metabolism (VT′), differences of 10%–16% were observed, with women greater than men. In contrast, when regional brain activity was normalized to free plasma parent (VT), there was less than a 4% difference by sex in regional brain β2-nAChR availability. These sex differences in kBq/cm3 and VT′ resulted from significantly higher levels of total plasma parent, free fraction (f1), and free plasma parent in women than in men nonsmokers. No differences in plasma measures or brain β2-nAChR availability were observed across the menstrual cycle for any outcome measure. Conclusion: Overall, these findings demonstrate no significant difference in brain β2-nAChR availability between men and women nonsmokers or across the menstrual cycle. Importantly, these findings demonstrate sex differences in radiotracer metabolism and plasma protein binding and highlight the critical need to measure plasma radiotracer levels and f1 in studies that include both sexes.