Synthesis optimization of pittsburgh compound B by the captive solvent method

Abstract

Carbon-11 is a positron emitting nuclide that has been used extensively to label compounds destined for molecular targets in the brain. Pittsburgh compound B ([ 11 C]PiB) is a benzothiazole derivative of thioflavin T that is used to image beta-amyloid deposits in Alzheimer's disease patients with Positron Emission Tomography (PET). In this paper we report on the optimization of a fully automated synthesis, purification and reformulation of [ 11 C]PiB suitable for use in human PET studies. [ 11 C]PiB was prepared from 2-(4'-aminophenyl)-6-hydroxybenzothiazole by [ 11 C]-methylation with methyl triflate reacting in an high-performance liquid chromatography (HPLC) loop, purified and reformulated by solid phase extraction.The specific activity of [ 11 C]PiB was 25 ± 10 GBq/µmol, and radiochemical purity was better than 95%.

Impact of TOF on Brain PET With Short-Lived 11C-Labeled Tracers Among Suspected Patients With AD/PD: Using Hybrid PET/MRI

“…The hybrid PET/MRI, like two high-end technologies, can simultaneously obtain images of PET and MRI, which provide excellent anatomic information and functional MRI parameters with the metabolic and molecular information as a one-stop-shop. Therefore, the hybrid PET/MRI has always been used for neurodegenerative diseases, especially showing great potential for differential diagnosis of early AD/PD with some specific PET tracer (8)(9)(10). Among a tracer targeted dopamine transporters (DATs) level for early diagnosis of PD is 11 C labeled cocaine derivative, i.e., 11 C-2-ß-carbomethoxy-3-b-(4-fluorophenyl) tropane ( 11 C-CFT) (8).…”

“…In the patients with PD, the DATs level will change, and the PET images with 11 C-CFT will show the asymmetrical reduction in the caudate nucleus (CN) or putamen (PU). The Pittsburgh compound B, i.e., 2-(4-N-[ 11 C] methylaminophenyl)-6-hydroxybenzothiazole ( 11 C-PiB) is a benzothiazole derivative of thioflavin T that is used to image beta-amyloid deposits in AD (9), and the corresponding PET images with 11 C-PiB will show the diffuse uptake in the brain. However, the synthesis and quality control of 11 C-CFT and 11 C-PiB are complicated processes which are followed by high-performance liquid chromatography (HPLC) purification (9,10).…”

“…The Pittsburgh compound B, i.e., 2-(4-N-[ 11 C] methylaminophenyl)-6-hydroxybenzothiazole ( 11 C-PiB) is a benzothiazole derivative of thioflavin T that is used to image beta-amyloid deposits in AD (9), and the corresponding PET images with 11 C-PiB will show the diffuse uptake in the brain. However, the synthesis and quality control of 11 C-CFT and 11 C-PiB are complicated processes which are followed by high-performance liquid chromatography (HPLC) purification (9,10). As well, 11 C radioisotope tends to decay fast within a half-life (T 1/2 ) of 20.38 min.…”

Two decades of [11C]PiB synthesis, 2003-2023: a review

“…Oxygen and other radio impurities can be removed using a cryogenic trap (liquid nitrogen) in combination with molecular sieves prior to the radiosynthesis procedure [29,30]. Cyclotron-produced [ 11 C]CO 2 [31] and [ 11 C]CH 4 [24] have both been used for [ 11 C]PiB radiosynthesis.…”

“…[ 11 C]MeI is an established starting material in the production of 11 C labeled tracers [32][33][34] and it has been used for [ 11 C]PiB radiolabeling both directly [16] and as an intermediate [30,31,35]. The longstanding "wet" method for [ 11 drawback to the "wet method" is the fact that the LiAlH 4 solution can be a source of carbon-12 isotopic dilution, considerably lowering the MA of the final [ 11 C]PiB (with MA typically ranging 50-150 GBq/μmol) [20].…”