title: 5-HT1A sex based differences in Bmax, in vivo KD, and BPND in the nonhuman primate.
abstract: Serotonin (5-HT) dysfunction has been implicated in neuropsychiatric illnesses and may play a pivotal role in the differential prevalence of depression between the sexes. Previous PET studies have revealed sex-based differences in 5-HT1A binding potential (BPND). The binding potential is a function of the radioligand-receptor affinity (1/KDapp), and receptor density (Bmax). In this work, we use a multiple-injection (MI) PET protocol and the 5-HT1A receptor antagonist, [(18)F]mefway, to compare sex-based differences of in vivo affinity, Bmax, and BPND in rhesus monkeys.
  
  
  METHODS
  PET [(18)F]mefway studies were performed on 17 (6m, 11f) rhesus monkeys using a 3-injection protocol that included partial saturation injections of mefway. Compartmental modeling was performed using a model to account for non-tracer doses of mefway for the estimation of KDapp and Bmax. BPND estimates were also acquired from the first injection (high specific activity [(18)F]mefway, 90-minute duration) for comparison using the cerebellum (CB) as a reference region. Regions of interest were selected in 5-HT1A binding regions of the hippocampus (Hp), dorsal anterior cingulate cortex (dACC), amygdala (Am), and raphe nuclei (RN).
  
  
  RESULTS
  Female subjects displayed significantly (*p<0.05) lower KDapp in the Hp (-32%), Am (-38%), and RN (-37%). Only the Hp displayed significant differences in Bmax with females having a Bmax of -29% compared to males. Male subjects demonstrated significantly lower BPND measurements in the Am (14%) and RN (29%).
  
  
  CONCLUSIONS
  These results suggest that the higher BPND values found in females are the result of lower [(18)F]mefway KDapp. Although a more experimentally complex measurement, separate assay of KDapp and Bmax provides a more sensitive measure than BPND to identify the underlying differences between females and males in 5-HT1A function.
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison, WI 53705, USA. dwooten@wisc.edu
authors.forename: Dustin W
authors.initials: DW
authors.lastname: Wooten
authors.forename: Ansel T
authors.initials: AT
authors.lastname: Hillmer
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Moirano
authors.forename: Dana L
authors.initials: DL
authors.lastname: Tudorascu
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Ahlers
authors.forename: Maxim S
authors.initials: MS
authors.lastname: Slesarev
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Jogeshwar
authors.initials: J
authors.lastname: Mukherjee
authors.forename: Mary L
authors.initials: ML
authors.lastname: Schneider
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D007091:Image Processing, Computer-Assisted; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A
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