Abstract
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Objectives Noninvasive monitoring of tau protein aggregates will provide useful information regarding tau pathology in traumatic brain injury and diseases such as Alzheimer’s. [18F]THK-5117 and [18F]THK-5105 have shown high binding affinities to tau protein aggregates (Ki ~10 nM). Herein, we discuss their fully automated radiosyntheses using GE Tracerlab FXFN module.
Methods We performed automated radiosyntheses of [18F]THK-5117 and [18F]THK-5105 by modifying the reported manual procedures. The radiosynthesis involved the displacement of the tosylate-leaving group with Kryptofix/K2CO3 activated [18F]-fluoride, followed by acidic hydrolysis of the THP protecting group, neutralization and solid phase extraction before HPLC purification. The collected product fraction was diluted with water, passed through a tC18 cartridge. The final product was formulated and filtered into a pyrogen-free collection vial as an ethanol (10%) containing saline solution.
Results We initially isolated the [18F]-THK compounds in 20-30% yields. We found that addition of ascorbic acid in the previously reported procedure did not present any added value (no radiolysis was observed for 4 hr in its absence). Increasing water volume for dilution and eliminating the ascorbic acid improved the trapping of the labeled product on the tC18 cartridge. The final yields were increased to 68% for [18F]THK-5117 and 45-52% for [18F]THK-5105, with >99% chemical and radiochemical purity and 5±0.5 mCi/nmol of specific activity (EOS).
Conclusions The fully automated radiosyntheses of both THK compounds were successfully and efficiently achieved on a GE Tracerlab FXFN module with reproducible and improved yields. Preclinical imaging studies with microPET are underway.