M1 muscarinic acetylcholine receptors (mAChRs) are abundant in postsynaptic nerve terminals of all forebrain regions and have been implicated in the cognitive decline associated with Alzheimer’s disease and other CNS pathologies. Consequently, major efforts have been spent in the development of subtype-selective positron emission tomography (PET) tracers for mAChRs resulting in the development of several 11C-labeled probes. However, protocols for the preparation of 18F-labeled mAChR-ligands have not been published so far. Here, we describe a straightforward procedure for the preparation of an 18F-labeled M1 mAChR agonist and its corresponding pinacol boronate radiolabeling precursor and the non-radioactive reference compound. The target compounds were prepared from commercially available aryl fluorides and Boc protected 4-aminopiperidine using a convergent reaction protocol. The radiolabeling precursor was prepared by a modification of the Miyaura reaction and labeled via the alcohol-enhanced Cu-mediated radiofluorination. The developed procedure afforded the radiotracer in a non-decay-corrected radiochemical yield of 17 ± 3% (n = 3) and in excellent radiochemical purity (>99%) on a preparative scale. Taken together, we developed a straightforward protocol for the preparation of an 18F-labeled M1 mAChR agonist that is amenable for automation and thus provides an important step towards the routine production of a 18F-labeled M1 selective PET tracer for experimental and diagnostic applications.
Arylpropylsulphonamides are in the focus of research as a-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) receptor ligands. A new fluorine-18-labelled potentiator of AMPA receptors was synthesized as a potential radiotracer for cerebral imaging with positron emission tomography. Using N-2-(4-N-(4-nitrobenzamido)-phenyl)-propyl-2-propanesulphonamide (7) Optimization of the reaction parameters time, temperature, solvent and concentration gave a radiochemical yield of 38 AE 8% at 1808C in dimethylsulphoxide within 30-min reaction time. After a solid-phase extraction followed by a high-performance liquid chromatography separation, the product could be obtained in radiochemical yields of 5 AE 1.5%. Radiochemical purity was higher than 95% and the specific activity amounted to 77 AE 40 GBq/mmol. First in vitro assays with rat brain slices revealed a high non-specific binding and a uniform distribution of [ 18 F]8 not lending it for in vivo imaging purposes.
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