2-[18F]fluoro-A-85380, an in vivo tracer for the nicotinic acetylcholine receptors

Abstract

The in vivo brain regional distribution of 2-[18F]fluoro-A-85380, a novel tracer for positron emission tomographic (PET) studies, followed the regional densities of brain nAChRs reported in the literature. Evidence of binding to nAChRs and high specificity of the binding in vivo was demonstrated by inhibition with nAChR selective ligands as well as with unlabeled 2-fluoro-A-85380. A preliminary toxicology study of the 2-fluoro-A-85380 showed a relatively low biological effect. 2-[18F]Fluoro-A-85380 holds promise as a useful radiotracer for imaging of nAChRs with PET.

Functional brain imaging of tobacco use and dependence

“…Radiolabeling of A-85380 was a major advance in imaging nAChRs, because administration of radiolabeled nicotine (used for previous imaging studies) results in high non-specific binding and short drug-receptor interaction times (Sihver et al, 2000). In recent years, 2-[ 18 F]F-A-85380 or simply 2-FA and related compounds (Chefer et al, 1999;Horti et al, 1998;Koren et al, 1998) have been developed for PET imaging, and 5-[ 123/125 I] iodo-A85380 has been used for SPECT imaging (Chefer et al, 1998;Horti et al, 1999;Mukhin et al, 2000) of α 4 β 2 nAChRs.…”

Validation of an Extracerebral Reference Region Approach for the Quantification of Brain Nicotinic Acetylcholine Receptors in Squirrel Monkeys with PET and 2-18F-Fluoro-A-85380

“…18 F-Fluoride was produced by use of an RDS111 negative-ion cyclotron, and 2-FA was synthesized by use of a modified semiautomated method (9). The final product was formulated as a sterile and pyrogen-free isotonic solution.…”

Synthesis of 6‐chloro‐3‐((2‐(S)‐azetidinyl)methoxy)‐5‐(2‐[18F]fluoropyridin‐4‐yl)pyridine ([18F]NIDA 522131), a novel potential radioligand for studying extrathalamic nicotinic acetylcholine receptors by PET

“…18 F]-labelled 1b ( Figure 1) was performed initially by the no-carrier-added nucleophilic Kryptofix 222 -assisted halogen-exchange radiofluorination of compound 2 followed by removal of tert-BOC-protective group using a general procedure described previously 12 (Scheme 2). Incorporation of radiofluoride via precursor 2 was optimized with respect of reaction temperature (optimal temperature 1858C, temperature range 18 F]NIDA522131 were both purified by semi-preparative high-performance liquid chromatography (HPLC).…”

“…Previously, we found that 2-iodopyridine derivatives can be radiofluorinated successfully with high radiochemical yield. 12 Compound 3 was synthesized through copper-assisted iodo-bromo-exchange reaction (Scheme 1). We did not observe any potential reaction of the iodo-chloro-exchange as was expected from previous studies.…”