N-[18F]4'-fluorobenzylpiperidin-4yl-(2-fluorophenyl) acetamide ([18F]FBFPA): a potential fluorine-18 labeled PET radiotracer for imaging sigma-1 receptors in the CNS.
A series of brain uptake studies and PET imaging studies were conducted with the sigma(1) selective imaging agent, [(18)F]FBFPA. The results of the study indicate that this radiotracer readily crosses the blood-brain barrier and labels sigma(1) receptors in vivo. In vivo blocking studies with a sigma(1) selective ligand and a nonselective sigma(1)/sigma(2) receptor ligand indicates that [(18)F]FBFPA labels sigma(1) and not sigma(2) receptors in rodent brain. PET imaging studies demonstrated a high uptake in regions of rhesus monkey brain having a high density of sigma(1) receptors. The uptake of [(18)F]FBFPA was displaced by the sigma ligand, haloperidol (1 mg/kg, i.v.). In vivo blocking studies indicate that the progesterone blocked the brain uptake of [(18)F]FBFPA in rat brain. These data indicate that [(18)F]FBFPA is a potential radiotracer for imaging sigma(1) receptors in the CNS in vivo with PET.
Mach
Robert H
RH
Department of Radiology-PET Center Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. rhmach@mir.wustl.edu
Gage
H Donald
HD
Buchheimer
Nancy
N
Huang
Yunsheng
Y
Kuhner
Ross
R
Wu
Li
L
Morton
Thomas E
TE
Ehrenkaufer
Richard L
RL
D000081:Acetamides / Q000138:chemical synthesis; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D006220:Haloperidol / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000378:metabolism*; D000097605:Sigma-1 Receptor
D000081:Acetamides; D018492:Dopamine Antagonists; D005462:Fluorine Radioisotopes; D006220:Haloperidol; D011374:Progesterone; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor