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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 versio...

Abstract. Molecular imaging is usually based on the recognition by the radiopharmaceuticals of specific sites which are present in limited number or density in the cells or biological tissues. Thus is of high importance to label the radiopharmaceuticals with high specific activity to be able to achieve a high target to non target ratio. The presence of carbon dioxide (CO 2 ) from the air containing 98,88% of 12 C and 1,12% 13 C compete with 11 CO 2 produced at the cyclotron. In order to minimize the presence of these isotopes along the process of irradiation, transferring and synthesis of radiopharmaceuticals labelled with 11 C, we applied this method: previous to the irradiation the target was 3-4 times flushed with He (5.7) as a cold cleaning, followed by a similar conditioning of the line, from the target up to the module, and finally a hot cleaning in order to desorb 12 CO 2 and 13 CO 2 , this was performed by irradiation during 1 min at 5 uA (3 times). In addition, with the aim of improving quality of gases in the target and in the modules, water traps (Agilent) were incorporated in the inlet lines of the target and modules. Target conditioning process (cold and hot flushings) as well as line cleaning, allowing the desorption of unlabelled CO 2 , together with the increasing of gas purity in the irradiation and in the synthesis, were critical parameters that enable to achieve 11 C-radiopharamaceuticals with high specific activity, mainly in the case of 11 C-PIB.

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