Radiosynthesis of the D2/3 agonist [3-11C]-(+)-PHNO using [11C]iodomethane

We report here a radiosynthesis for the D2/3 agonist (+)-4-([3-11C]propyl)-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (3-[11C]-(+)-PHNO) labelled at the terminal carbon of the N-propyl chain. The protocol is based on 11C-methylation of an N-acetyl precursor. This initial step is followed by a reduction with LiAlH4 to give ([3-11C]-(+)-PHNO). We first applied the method for the synthesis of a model compound, N-3-([11C]propyl)-1,2,3,4-tetrahydroisoquinoline, which we obtained in 77–97% analytical radiochemical yield (n=6) in 20 min. Similarly, we prepared ([3-11C]-(+)-PHNO) in 55–60% analytical radiochemical yield (n=5) using a one-pot procedure. We have also been able to implement the complete process on a semi-automated module. This platform delivered purified and formulated [3-11C]PHNO with an average radiochemical yield of 9% (n=13, range 2–30%, non-decay corrected), a radiochemical purity >95%, and a specific radioactivity of 26.8–81.1 GBq/μmol in a total time of 63–65 min.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We report an alternative method to obtain carbon-11 labelled PHNO. ► The method is based on readily available [11C]methyl iodide as starting material. ► We have automated the alkylation/reduction protocol including purification and formulation.