Synthesis procedure for routine production of 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A-85380).

2-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A-85380) was among the first subtype selective radioligands to visualise the in vivo distribution of alpha4beta2-containing neuronal nicotinic acetylcholine receptors (nAChRs) in human brain. We developed a one-pot synthesis for the preparation of 2-[18F]F-A-85380 in a commercially available TRACERlab FXF-N synthesis module. The synthesis comprises a nucleophilic substitution followed by hydrolysis of a t-butyloxycarbonyl (BOC)-protected intermediate. After formulation for intravenous application up to 20 G Bq 2-[18F]F-A-85380 were produced from a starting activity of 100 G Bq [18F]fluoride in 60 min with a specific activity of about 4.10(5)GBq/mmol and a mean radiochemical purity of more than 99%.

[1]  C. Crouzel,et al.  Synthesis of 2‐[18F]fluoro‐3‐[2(S)‐2‐azetidinylmethoxy]pyridine, a highly potent radioligand for in vivo imaging central nicotinic acetylcholine receptors , 1998 .

[2]  P. Falkai,et al.  Imaging of central nAChReceptors with 2-[18F]F-A85380: optimized synthesis and in vitro evaluation in Alzheimer's disease. , 2004, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[3]  J. Steinbach,et al.  Autoradiography of 2‐[18F]F‐A‐85380 on nicotinic acetylcholine receptors in the porcine brain in vitro , 2006, Synapse.

[4]  C Crouzel,et al.  Synthesis and nicotinic acetylcholine receptor in vivo binding properties of 2-fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine: a new positron emission tomography ligand for nicotinic receptors. , 1999, Journal of medicinal chemistry.

[5]  C. Gotti,et al.  Neuronal nicotinic receptors: from structure to pathology , 2004, Progress in Neurobiology.

[6]  K. Kellar,et al.  Pharmacology of the agonist binding sites of rat neuronal nicotinic receptor subtypes expressed in HEK 293 cells. , 2004, Bioorganic & medicinal chemistry letters.

[7]  D Wyper,et al.  Nicotinic Acetylcholine Receptor Distribution in Alzheimer's Disease, Dementia with Lewy Bodies, Parkinson's Disease, and Vascular Dementia: In Vitro Binding Study Using 5-[125I]-A-85380 , 2004, Neuropsychopharmacology.

[8]  D. Donnelly-roberts,et al.  Novel 3-Pyridyl ethers with subnanomolar affinity for central neuronal nicotinic acetylcholine receptors. , 1996, Journal of medicinal chemistry.

[9]  Jean-Dominique Gallezot,et al.  In vivo imaging of human cerebral nicotinic acetylcholine receptors with 2-18F-fluoro-A-85380 and PET. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  F. Jessen,et al.  A simple and fast method for the preparation of n.c.a. 2-[18F]F-A85380 for human use. , 2005, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[11]  M. Quik,et al.  Nicotine and nicotinic receptors; relevance to Parkinson's disease. , 2002, Neurotoxicology.