Abstract
1039
Objectives: Tau PET tracers are well known radioactive probes designed for imaging of the accumulation and regional spread of brain neurofibrillary tangles (NFTs). NFTs are characteristic of neurodegenerative disorders known as tauopathies, Alzheimer’s disease (AD) being the most common. Second generation Tau tracers, such as [18F]MK-6240, have recently been developed to improve their binding properties and lower the off-target binding. First in human studies with [18F]MK-6240 underlined it as a promising PET radioligand for in vivo imaging of neurofibrillary tau aggregates in AD with minimal off-target binding in the human brain. The purpose of this work is to develop the automation of [18F]MK-6240 production on a cassette-based platform and enable its routine production and distribution at large scale.
Methods: The production of [18F]MK-6240 is performed along the synthesis method described hereafter (Figure 1) and performed with an AllinONe with HPLC following the cassette layout depicted below (Figure 2). The 18F- produced in the cyclotron is separated from the aqueous solvent by trapping on an anion-exchange cartridge followed by elution with a solution of tetrabutylammonium hydrogen bicarbonate (TBAHCO3) to give the intermediate (2). The precursor (1) is added to the intermediate (2). Heating the reaction to 160°C in DMF allows, in addition to the radiolabelling , the thermal to afford the crude [18F]MK-6240 radiotracer in one single step (3). [18F]MK-6240 (3) is purified by a reversed phase semi-preparative HPLC. The fraction of interest is collected and reformulated on a SPE cartridge. The product is ready for QC and dispensing.
Results: [18F]MK-6240 was produced on the Trasis AllinOne unit- in 65 minutes (from start of the synthesis to the collection in the final vial) - with a typical average yield of 30 +- 5 % non-decay-corrected (NDC) (53 +-7 % decay corrected) The HPLC purification was performed on the integrated HPLC unit and allows to selectively collect the [18F]MK-6240 peak, as depicted below on the chromatogram (Figure 3). Stability of the final product was tested up to ~ 30 GBq and demonstrated >98% RCP at 8 hours post EOS. [18F]MK-6240 Synthesis have been performed on different Trasis synthesizers, at different facilities and with several operators and gave similar results, highlighting the robustness of the process.
Conclusions: The automation of the 18F]MK-6240 PET tracer synthesis on the AllinOne platform afford a reliable cassette-based synthesis, providing high yields (30+-5% NDC) and a stable product over time.
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.