Development of a radioligand for imaging V-1a vasopressin receptors with PET

作者：Naik Ravi; Valentine Heather; Hall Andrew; Mathews William B; Harris James C; Carter C Sue; Dannals Robert F; Wong Dean F; Horti Andrew G^*

来源：European Journal of Medicinal Chemistry, 2017, 139: 644-656.

DOI：10.1016/j.ejmech.2017.08.037

• Vasopressin receptor
• Positron emission tomography
• Radiotracers

A series of vasopressin receptor V-1a ligands have been synthesized for positron emission tomography (PET) imaging. The lead compound (1S,5R)-1 ((4-(1H-indo1-3-y1)-3-methoxyphenyl) ((1S,5R)-1,3,3trimethy1-6-azabicyclo[3.2.1]octan-6-yemethanone) and its F-ethyl analog 6c exhibited the best combination of high binding affinity and optimal lipophilicity within the series. (1.5,5R)-1 was radiolabeled with C-11 for PET studies. [(CH3)-C-11](1S,5R)-1 readily entered the mouse (4.7%113/g tissue) and prairie vole brains (similar to 2% ID/g tissue) and specifically (30-34%) labeled Via receptor. The common animal anesthetic Propofol significantly blocked the brain uptake of [(CH3)-C-11](1S,5R)-1 in the mouse brain, whereas anesthetics Ketamine and Saffan increased the uptake variability. Future PET imaging studies with Via radiotracers in non-human primates should be performed in awake animals or using anesthetics that do not affect the V-1a receptor.

• 出版日期2017-10-20