Synthesis of 1,3,4,6-Tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose (Mannose Triflate) Precursor for the Production of [18F] FDG.

Abstract

Purpose of the study: 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose (mannose triflate), the precursor used for the synthesis of [¹⁸F] Fluorodeoxyglucose ([¹⁸F] FDG) is imported from a few commercial suppliers abroad. As part of self-reliance, a reliable synthesis and characterization of mannose triflate has been developed, details of which are reported in this paper.

Materials and methods: Synthesis of 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose (Mannose triflate) carried by Triflation of 1,3,4,6-Tetra-O-acetyl-β-D-mannopyranose with Tf2O-pyridine under argon atmosphere for 6 h. Synthesized mannose triflate is used for the production of [¹⁸F] FDG using siemens explora FDG-4-automated module.

Results: Starting from 2.6 g of 1,3,4,6-Tetra-O-acetyl-β-D-mannopyranose, mannose triflate was synthesized with an overall yield of ~ 3.0 g (~80%). The synthesis was systematically scaled up to 52 g based on the experience from the initial small size batches. The characterization of the product was done by Infra Red, Nuclear Magnetic Resonance and Mass spectroscopy. The precursor was used in the manufacture of [¹⁸F] FDG using Siemens Explora synthesis module. Radiochemical yields of 55% ± 2% (decay uncorrected), radiochemical purity >96% were obtained which is comparable with the imported precursor. All the quality control parameters were within the limits as per pharmacopoeia when the in-house synthesized mannose triflate was used.

Conclusion: A large-scale preparation of mannose triflate is now carried out to satisfy the growing needs for FDG in positron emission tomography centers and hospitals.