Production of [18F]NAV4694 on an FX2N synthesis module for imaging amyloid plaques

Introduction: Amyloid PET imaging has changed the management of Alzheimer's disease patients. Several radiopharmaceuticals have evolved in the last two decades. We are reporting the synthesis of the amyloid imaging PET tracer fluorine-18[¹⁸F]NAV4694 in the FX2N synthesis module under GMP-compliant conditions for clinical use.

Methods: The radiosynthesis was standardised in the FX2N synthesis module, and the precursor concentration was varied from 0.5 to 2.0 mg for labelling with ¹⁸F at 110 °C, with a reaction time of 5-10 min, followed by hydrolysis with 0.6 M HCl for 5 min. The final purification was standardised with various C18 cartridges to get the maximum yield. All standard quality controls were performed, along with in vivo stability. Briefly, 350 ± 50 MBq of the [¹⁸F]NAV4694 was injected intravenously in patients, and PET-MR imaging was performed. The images were processed, and the distribution of the tracer was visually observed in the brain.

Results: A minimum of 2 mg concentration was found to be suitable for radiolabeling at 110 °C for 10 min and purified via C18 plus long cartridge, providing the highest radiochemical yield of 13 ± 3 % (decay corrected). The radiochemical purity was 99 ± 0.5 % with a molar activity of 255 ± 125 GBq/μmol. The retention time of the [¹⁸F]NAV4694 was 17.6 ± 0.8 min, which was consistent with the UV/Vis peak of cold NAV4694 at 17.4 ± 0.7 min. The residual Solvents, like DMSO and ethanol, were less than the prescribed limit. The HPLC (from plasma) showed no primary metabolites in the plasma, and the stability was 96 ± 2 % (in vitro) and 94 ± 2 % (in vivo). The human biodistribution showed a rapid clearance from the blood. The visual analysis showed uptake in cortical grey matter in a positive amyloid scan and in white matter in an amyloid-negative scan.

Conclusion: [¹⁸F]NAV4694 was successfully synthesised in the FX2N synthesis module with high radiochemical purity. It showed distinctive uptake patterns in amyloid-positive and negative scans.

Amyloid PET; Fluorine-18; NAV4694; PET imaging; Radiochemistry.