- Synthesis of a radiotracer for studying nicotinic acetylcholine receptors: 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]A- 85380)
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The radiochemical synthesis of 2-[18F]fluoro-3-(2(S)- azetidinylmethoxy)pyridine (2-[18F]A-85380, [18F]1) was accomplished by Kryptofix 222 assisted nucleophilic no-carrier-added [18F]fluorination of 2-iodo-3-((1-tert-butoxycarbonyl-2(S)-azetidinyl)methoxy)pyridine, 2 followed by acidic deprotection. The average radiochemical yield was 10% and the average specific radioactivity was 1050 mCi/μmol, calculated at end-of- synthesis (EOS).
- Horti, Andrew G.,Koren, Andrei O.,Ravert, Hayden T.,Musachio, John L.,Mathews, William B.,London, Edythe D.,Dannals, Robert F.
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p. 309 - 318
(2007/10/03)
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- Synthesis of 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine, a highly potent radioligand for in vivo imaging central nicotinic acetylcholine receptors
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This paper reports the synthesis of 2-fluoro-3-[2(S)-2- azetidinylmethoxy]pyridine and its radiolabeling with fluorine-18 ([18F]FK- K222) by nucleophilic aromatic nitro-to-fluoro substitution in DMSO by conventional heating at 150°C for 20 min or by microwave activation at 100 Watt for 1 min. This fluoro compound is a closely related analog of the high affinity nicotinic ligand A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine). This compound is the lead compound of a novel 3-pyridyl ether series of new nAChR ligands recently published, and possesses not only subnanomolar comparable to that of epibatidine, for the α4β2 subtype, but also a weaker affinity for the other subtypes or nAChRs. 110-140 mCl (4.1-5.2 GBq) of pure 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ([18F]fluoro-A-85380) could be obtained in less than 2 hours, with specific radioactivities of 3-5 Ci/μmol (111-185 GBq/μmol) calculated for End of Bombardment (or 1.5-2.5 Ci/μmol (55.5-92.5 GBq/μmol) at End of Synthesis) for a 20 μA, 30 min (36000 μC) irradiation of a 95% enriched [18O]water target with a 16 MeV proton beam [18O(p,n)18F]. Yield (with respect to [18F]fluoride ion) : decay-corrected 49-64% ; non-decay corrected 25-33%. Total synthesis time from EOB : 105-110 min (this includes the recovery of the [18F]fluoride ion from the target and the [18F]FK-K222-complex preparation). Preliminary results in rats showed a substantial uptake of the ligand in the thalamus (1% I.D./g tissue at 30 min) while the cerebellar uptake was 2-fold lower. Thalamic uptake was reduced by 75-85% following a pre treatment with nicotine, cytisine, epibatidine or fluoro-A-85380. The full pharmacological profile and the potential for eventual clinical applications of this ligand as a tracer for PET experiments are currently under investigation.
- Dolle, Frederic,Valette, Heric,Bottlaender, Michel,Hinnen, Francoise,Vaufrey, Francoise,Guenther, Ilonka,Crouzel, Christian
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p. 451 - 463
(2007/10/03)
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