Fully-automated radiosynthesis of the amyloid tracer [11C] PiB via direct [11C]CO2 fixation-reduction

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. [ 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%). 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.