Radiosynthesis of ¹⁸F-labeled d-allose

Rare sugars are defined as monosaccharides that exist in nature but are only present in limited quantities. d-Allose is a rare sugar that has been reported to have some unique physiological effects. The present study describes suitable synthetic procedures for novel rare sugars of d-allose that are ¹⁸F-labeled at the C-3 and C-6 positions and the preparation of the appropriate labeling precursors. The goal is to facilitate in vivo, noninvasive positron emission tomography (PET) investigation of the behavior of rare sugar analogs of d-allose in organs. We found five precursors that were practical for labeling, three for 3-deoxy-3-[¹⁸F]fluoro-d-allose ([¹⁸F]3FDA) and two for 6-deoxy-6-[¹⁸F]fluoro-d-allose ([¹⁸F]6FDA). With manual operation synthesis, the highest radiochemical conversion rates were 75% for [¹⁸F]3FDA with a precursor of 1,2,4,6-tetra-O-acetyl-3-O-trifluoromethanesulfonyl-β-d-glucopyranose and 69% for [¹⁸F]6FDA with a precursor of 1,2,3,4-tetra-O-acetyl-6-O-trifluoromethanesulfonyl-β-d-allopyranose. Furthermore, the practical yields of [¹⁸F]3FDA and [¹⁸F]6FDA using an automated synthesizer were also investigated. Radiochemical yields of 67% and 49% were obtained for [¹⁸F]3FDA and [¹⁸F]6FDA, respectively, in an automated synthesizer. As basic assessment of stability for use in PET scanning, high performance liquid chromatography analysis showed no decomposition of [¹⁸F]3FDA and [¹⁸F]6FDA after up to 6 h in rabbit blood plasma.