RT Journal Article
SR Electronic
T1 Evaluation of serotonin receptors using 18F-trans-Mefway in aging canine model
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1196
OP 1196
VO 50
IS supplement 2
A1 Thuynhi Dinh
A1 Sara Faheem
A1 Neerva Rana
A1 Neil Saigal
A1 Suresh Pandey
A1 Elizabeth Head
A1 Jogeshwar Mukherjee
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1196.abstract
AB 1196 Objectives Serotonin 5HT1A receptors are implicated in neurological and psychiatric disorders including aging and Alzheimer’s disease (AD). We report the in vitro use of 18F-trans-Mefway (Mefway; Ki=3.11 nM) as an imaging agent in canine model for AD (Head et al.,2008). Methods Radiosynthesis of Mefway was carried out with a specific activity of >2 Ci/mmol (Saigal et al., 2006). Brain tissue was obtained from male Sprague-Dawley rats, B6SJLF1mice and beagle dogs. Ages of the dogs varied from 1 to 15.4 years (equivalent to ~15 to 90 human years). Sections (10 μm thick) of the tissue were obtained including the cortex (COR) and cerebellum (CB). Sections were preincubated at room temperature for 15 min in 50 mM Tris-HCl buffer (pH 7.4). Incubation with 1.5 μCi/cc of Mefway at 37 oC took place for 1 hour. Nonspecific binding was with 10 μm serotonin. Post incubation, sections were washed twice for 3 min in cold buffer, submerged quickly in cold distilled water and laid out to dry and exposed to phosphor films and quantified. Results Binding of Mefway in the various brain regions of mice, rats and dogs were consistent. Serotonin displaced >90% of binding. The CB of each model was used as reference in ratio measurements. Ratios were: Mice: COR/CB=14; Rats: COR/CB= 22; 1 Yr Dog: COR/CB= 19. Canine cortex exhibited highest binding in layers I,II (100%) and least in III,IV(31%), similar to that found in humans. Presence of Aβ16 was confirmed immunosatined cortical layers of older dog brain with little effect on Mefway binding. Further studies are underway in additional old animals. Conclusions Mefway is suitable for evaluation of 5HT1A receptors in animal models of aging and AD.