Convenient synthesis of 18F-radiolabeled R-(-)-N-n-propyl-2-(3-fluoropropanoxy-11-hydroxynoraporphine.
Aporphines are attractive candidates for imaging D2 receptor function because, as agonists rather than antagonists, they are selective for the receptor in the high affinity state. In contrast, D2 antagonists do not distinguish between the high and low affinity states, and in vitro data suggests that this distinction may be important in studying diseases characterized by D2 dysregulation, such as schizophrenia and Parkinson's disease. Accordingly, MCL-536 (R-(-)-N-n-propyl-2-(3-[(18)F]fluoropropanoxy-11-hydroxynoraporphine) was selected for labeling with (18)F based on in vitro data obtained for the non-radioactive ((19)F) compound. Fluorine-18-labeled MCL-536 was synthesized in 70% radiochemical yield, >99% radiochemical purity, and specific activity of 167 GBq/µmol (4.5 Ci/µmol) using p-toluenesulfonyl (tosyl) both as a novel protecting group for the phenol and a leaving group for the radiofluorination.
Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA, 02478-9106, USA.
Anna W
AW
Sromek
Shaohui
S
Zhang
Vamsidhar
V
Akurathi
Alan B
AB
Packard
Wei
W
Li
David
D
Alagille
Thomas J
TJ
Morley
Ronald
R
Baldwin
Gilles
G
Tamagnan
John L
JL
Neumeyer
D001058:Apomorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D001060:Aporphines / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D005462:Fluorine Radioisotopes; D008024:Ligands; D057054:Molecular Imaging; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013237:Stereoisomerism
D001060:Aporphines; D005462:Fluorine Radioisotopes; D008024:Ligands; C000600252:N-n-propyl-2-(3-fluoropropanoxy-11-hydroxynoraporphine; D011166:Porphyrins; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; C081279:aporphine; C107018:porphine; D001058:Apomorphine
D2 agonist; D2high; D2low; aporphines; dopamine receptors; fluorine-18; neurological disorders; phenol protection; positron emission tomography; tosyl group