High-yield, automated radiosynthesis of 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) ready for animal or human administration.
The biomarker 2-(1-{6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([(18)F]FDDNP) is used as a positron emission tomography (PET) imaging probe for Alzheimer's disease and other neurodegenerative diseases. A high-yield and fully automated synthesis of [(18)F]FDDNP--along with the synthesis and characterization of non-radioactive FDDNP, a fluorescent probe derived from 2-(1,1-dicyanopropenyl-2)-6-dimethylaminonaphthalene (DDNP)--are reported. Radiofluorination of the tosyloxy precursor 2-{[6-(2,2-dicyano-1-methylvinyl)-2-naphthyl](methyl)amino}ethyl-4-methylbenzenesulfonate (DDNPTs) with K(18)F/Kryptofix 2.2.2. yielded chemically (>99%) and radiochemically (>99%) pure [(18)F]FDDNP in high radiochemical yields (40-60%; n> 120), with specific activities ranging from 4 to 8 Ci/mumol at the end of synthesis (90 minutes). Both remote, semiautomated and automated synthesis procedures are described. Either approach provides a reliable method for production of large quantities (110-170 mCi from 500 mCi of [(18)F]fluoride) of [(18)F]FDDNP allowing for multiple PET experiments in the same day or for distribution of the tracer from a single cyclotron facility to PET imaging centers at various geographical distances.
Liu
Jie
J
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, 10833 Le Conte Avenue CHS B2-086, Los Angeles, CA 90095, USA.
Kepe
Vladimir
V
Zabjek
Alenka
A
Petric
Andrej
A
Padgett
Henry C
HC
Satyamurthy
Nagichettiar
N
Barrio
Jorge R
JR
D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000181:Acrylonitrile / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D001331:Automation / Q000295:instrumentation / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
C116723:2-(1,1-dicyanopropenyl-2-)-6-dimethylaminonaphthaleney; C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D005462:Fluorine Radioisotopes; D009570:Nitriles; D019275:Radiopharmaceuticals; D015081:2-Naphthylamine; D000181:Acrylonitrile