Fully-automated radiosynthesis of the amyloid tracer [(11)C] PiB via direct [(11)C]CO(2) fixation-reduction

BACKGROUND: The β-amyloid radiotracer [(11)C] PiB is extensively used for the Positron Emission Tomography (PET) diagnosis of Alzheimer’s Disease and related dementias. For clinical use, [(11)C] PiB is produced using the (11)C-methylation method ([(11)C] Methyl iodide or [(11)C] methyl triflate as (11)C-methylation agents), which represents the most employed (11)C-labelling strategy for the synthesis of (11)C-radiopharmaceuticals. Recently, the use of direct [(11)C]CO(2) fixation for the syntheses of (11)C-tracers has gained interest in the radiochemical community due to its importance in terms of radiochemical versatility and for permitting the direct employment of the cyclotron-produced precursor [(11)C]CO(2). This paper presents an optimised alternative one-pot methodology of [(11)C]CO(2) fixation-reduction for the rapid synthesis of [(11)C] PiB using an automated commercial platform and its quality control. RESULTS: [(11)C] PiB was obtained from a (25.9 ± 13.2)% (Average ± Variation Coefficient, n = 3) (end of synthesis, decay corrected) radiochemical yield from trapped [(11)C]CO(2) after 1 min of labelling time using PhSiH(3) / TBAF as the fixation-reduction system in Diglyme at 150 °C. The radiochemical purity was higher than 95% in all cases, and the molar activity was (61.4 ± 1.6) GBq/μmol. The radiochemical yield and activity (EOS) of formulated [(11)C] PiB from cyclotron-produced [(11)C]CO(2) was (14.8 ± 12.1)%, decay corrected) and 9.88 GBq (± 6.0%), respectively. These are higher values compared to that of the (11)C-methylation method with [(11)C]CH(3)OTf (~ 8.3%). CONCLUSIONS: The viability of the system PhSiH(3) / TBAF to efficiently promote the radiosynthesis of [(11)C] PiB via direct [(11)C]CO(2) fixation-reduction has been demonstrated. [(11)C] PiB was obtained through a fully automated radiosynthesis with a satisfactory yield, purity and molar activity. According to the results, the one-pot methodology employed could reliably yield sufficiently high tracer amounts for preclinical and clinical use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s41181-019-0065-4) contains supplementary material, which is available to authorized users.