Fully Automated Radiosynthesis of [18f]lbt999on Tracerlab Fxfn and Allinonemodules, A Pet Radiopharmaceutical for Imaging the Dopamine Transporter in Human Brain

Background:Fluorine labelled 8-((E)-4-fluoro-but-2-enyl)-3b-p-tolyl-8-aza-bicyclo[3.2.1]octane-2b-carboxylic acid methyl ester ([18F]LBT999) is a selective radioligand for in vivoneuroimaging and quantification of the dopamine transporter by Positron Emission Tomography (PET). [18F]LBT999 has been produced on a TRACERlabFXFN for the Phase I study but forPhase III and a potent industrial production transfer, production has been also implemented on AllinOne (AIO)system requiring single use cassette. Both productions methods are reported herein. Results:Automation of [18F]LBT999radiosynthesis on FXFN was carried out in 35% yield (decay-corrected) in 65 min (n=16), with a radiochemical purity higher than 99 %and a molar activity of 158GBq/µmol at the end of synthesis. The transfer on the AIO platform followed by optimizations allowed the production of [18F]LBT999 in 32.7% yield (decay-corrected) within 48 min (n=5), with a radiochemical purity better than 98% and a molar activity in average higher to 154 GBq/µmol at the end of synthesis. Quality controls of both methods met the specification for clinical application.Conclusion:Both modules allow efficient and reproducible radiosynthesis of [18F]LBT999 with good radiochemical yields and a reasonable synthesis time.The developments made on AIO as its ability to meet pharmaceutical criteria and to more easily comply with GMP requirements make this approach as the best for a potent industrial production of the [18F]LBT999 and a future wider use.