Nucleophilic radiosynthesis of 2-[18F]fluoro-2-deoxy-D-galactose from Talose triflate and biodistribution in a porcine model

Abstract

Introduction: The galactose analogue 2-[(18)F]fluoro-2-deoxy-D-galactose (FDGal) is a promising positron emission tomography (PET) tracer for studies of regional differences in liver metabolic function and for clinical evaluation of patients with liver cirrhosis and patients undergoing treatment of liver diseases. However, there is an unmet need for routine production of FDGal from readily available starting material. In this study, we present the preparation of FDGal with high radiochemical purity and in amounts sufficient for clinical investigations from commercially available Talose triflate (1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-talopyranose). In addition, the biodistribution of FDGal in the pig is presented.

Methods: FDGal was prepared by nucleophilic fluorination of Talose triflate followed by basic hydrolysis. The entire synthesis was performed using the GE TRACERlab MX 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) synthesizer and existing methods for quality control of FDG were applied. Biodistribution of FDGal was studied by successive whole-body PET recordings of two anaesthetized 37-kg pigs.

Results: Up to 3.7 GBq sterile, pyrogen-free and no-carrier-added FDGal was produced with a radiochemical yield of 3.8±1.2% and a radiochemical purity of 98±1% (42 productions; yield is decay corrected). The adopted quality control methods for FDG were directly applicable for FDGal. Biodistribution studies in the pig revealed the liver and the urinary bladder as critical organs in terms of radiation dose.

Conclusion: Commercially available Talose triflate is a suitable starting material for routine productions of FDGal. The presented radiosynthesis and quality control methods allow for the production of pure, no-carrier-added FDGal in sufficient amounts for clinical PET-investigations of the liver.

Fig. 1

Typical quality control HPLC chromatograms for FDGal. Black traces are signals from the electrochemical detector, while blue traces are signals from the radio-detector: (A) Chromatograms of final solution on Dionex Carbopac PA1. (B) Chromatograms of final solution spiked with authentic FDGal on Dionex Carbopac PA1. (C) Radio-chromatogram of final solution on amino sugar column.

Fig. 1

Typical quality control HPLC chromatograms for FDGal. Black traces are signals from the electrochemical detector, while blue traces are signals from the radio-detector: (A) Chromatograms of final solution on Dionex Carbopac PA1. (B) Chromatograms of final solution spiked with authentic FDGal on Dionex Carbopac PA1. (C) Radio-chromatogram of final solution on amino sugar column.

Fig. 2

FDGal PET image of mean radioactivity concentration recorded 52–115 min after injection of 155 MBq FDGal to Pig #1 (37 kg; anaesthesia was induced with midazolam and ketamine-HCl and maintained by isoflurane and O₂/N₂O). The image shows maximum intensity projections. The activities in the liver, kidneys and urine bladder were high compared with other organs.

Fig. 3

Radioactivity concentration time courses in various organs as indicated after intravenous administration of FDGal. Data was obtained from the experiment illustrated in Fig. 2 (without correction for decay) and extrapolated from pig (37 kg) to human (74 kg) data.

Scheme 1

Radiosynthesis of FDGal by nucleophilic fluorination of Talose triflate.