This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We successfully synthesized four variations of lead candidate PET compounds, including unlabeled fluorinated and iodinated versions. We determined the relative affinity of the test compounds for human vasopressin and oxytocin receptor. Results indicated that each of the modified versions of lead compound was highly selective for human oxytocin receptor, with binding affinities 500 nM for human vasopressin receptor. Our candidate fluorine-18 ligand was labeled and subjected to tissue harvest studies using rat models. Results for brain penetration were inconclusive and log P values were again found to be in desired range. We opted to perform in vivo PET scans using rat models on our microPET/CT scanner. PET scans on four rats displayed no brain penetration, but significant uptake of ligand appeared in the pituitary gland where oxytocin and vasopressin are stored prior to peripheral release. Our candidate carbon-11 ligand was labeled and investigated in rat model via microPET/CT. Once again the lipophilicity was found to be in desired range, and despite having lowest molecular weight of all candidates, the compound did not display penetration into the brain. We were disappointed in initial results but believe that we have a sound plan to continue and are optimistic that we will succeed in developing a PET ligand. Plan includes trying to permeablize the blood-brain barrier by co-injection mannitol, as well as producing derivatives of other small molecule ligands with smaller molecular weights or there is evidence of penetration of the blood brain barrier.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000165-51
Application #
8357539
Study Section
Special Emphasis Panel (ZRR1-CM-5 (01))
Project Start
2011-08-01
Project End
2012-04-30
Budget Start
2011-08-01
Budget End
2012-04-30
Support Year
51
Fiscal Year
2011
Total Cost
$41,159
Indirect Cost
Name
Emory University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Maddox, S A; Kilaru, V; Shin, J et al. (2017) Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD. Mol Psychiatry :
Banerjee, Sunayana B; Gutzeit, Vanessa A; Baman, Justin et al. (2017) Perineuronal Nets in the Adult Sensory Cortex Are Necessary for Fear Learning. Neuron 95:169-179.e3
Bruner, Emiliano; Preuss, Todd M; Chen, Xu et al. (2017) Evidence for expansion of the precuneus in human evolution. Brain Struct Funct 222:1053-1060
Chen, Guiqin; Nie, Shuke; Han, Chao et al. (2017) Antidyskinetic Effects of MEK Inhibitor Are Associated with Multiple Neurochemical Alterations in the Striatum of Hemiparkinsonian Rats. Front Neurosci 11:112
Dehkharghani, S; Fleischer, C C; Qiu, D et al. (2017) Cerebral Temperature Dysregulation: MR Thermographic Monitoring in a Nonhuman Primate Study of Acute Ischemic Stroke. AJNR Am J Neuroradiol 38:712-720
Walker, Lary C; Jucker, Mathias (2017) The Exceptional Vulnerability of Humans to Alzheimer's Disease. Trends Mol Med 23:534-545
Payne, Christa; Cirilli, Laetitia; Bachevalier, Jocelyne (2017) An MRI study of the corpus callosum in monkeys: Developmental trajectories and effects of neonatal hippocampal and amygdala lesions. Dev Psychobiol 59:495-506
Tedesco, Dana; Thapa, Manoj; Gumber, Sanjeev et al. (2017) CD4(+) Foxp3(+) T cells promote aberrant immunoglobulin G production and maintain CD8(+) T-cell suppression during chronic liver disease. Hepatology 65:661-677
Hecht, E E; Mahovetz, L M; Preuss, T M et al. (2017) A neuroanatomical predictor of mirror self-recognition in chimpanzees. Soc Cogn Affect Neurosci 12:37-48
Fonseca, Jairo A; McCaffery, Jessica N; Kashentseva, Elena et al. (2017) A prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice. Vaccine 35:3239-3248

Showing the most recent 10 out of 880 publications