Synthesis optimization of 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB), β-amyloid PET imaging tracer for Alzheimer's disease diagnosis.

[11C]PIB is the most used amyloid plaques-specific positron-emitting radiotracers. The radiosynthesis of this compound, carried out by methylation of its precursor with [11C]methyl triflate in 2-butanone, has been improved optimizing the initial concentration and the purification method. Two HPLC methods were compared: good radiochemical yields, specific activities, and chemical purity above 98% were achieved by using as eluant acetonitrile/citrate and formulation in 10% ethanol.

Coliva A ，Monterisi C ，Apollaro A ，Gatti D ，Penso M ，Gianolli L ，Perani D ，Gilardi MC ，Carpinelli A ... -  《-》

Optimization of the radiosynthesis of the Alzheimer tracer 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB).

[(11)C]PIB is still the standard PET compound for Alzheimer imaging targeting beta-amyloid plaques. We aimed to establish a fully-automated procedure for the synthesis and purification of [(11)C]PIB with a high degree of reliability and improved specific activity as well as a suitable and fast quality control assay. The optimum reaction conditions were 75°C, 4 mg/mL precursor yielding at 48.0±2.7% (EOS, based on [(11)C]CH(3)OTf, corrected for decay), 183±14 GBq/μmol specific activity and >99% radiochemical purity. Time consumption was kept to a minimum (40 min from EOB) and overall yields were enough to serve 2 consecutive patients with a single preparation.

Philippe C ，Haeusler D ，Mitterhauser M ，Ungersboeck J ，Viernstein H ，Dudczak R ，Wadsak W ... -  《-》

Automated Synthesis of [(11)C]PiB via [(11)CH(3)OTf]-as Methylating Agent for PET Imaging of β-Amyloid.

Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [11C]PiB using commercially available dedicated [11C]- Chemistry module from the synthesized precursor. [11C]PiB is a promising radiotracer for PET imaging of β-Amyloid, advancing Alzheimer's disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [11C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [11C]PiB was purified via solid-phase methodology, and its quality control was performed by the quality and safety criteria required for clinical use. The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods were characterized all synthesized compounds. The fully automated [11C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [11C]PiB with [11C]CH3OTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life. The precursor for radiosynthesis of [11C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [11C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/μmol range. A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [11C]MeOTf as a methylating agent to synthesize [11C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center.

Singh AK ，Gambhir S ，Dixit M 《-》

Efficient radiosynthesis of carbon-11 labelled uncharged Thioflavin T derivatives using [11C]methyl triflate for beta-amyloid imaging in Alzheimer's Disease with PET.

Solbach C ，Uebele M ，Reischl G ，Machulla HJ ... -  《APPLIED RADIATION AND ISOTOPES》

Automated radiosynthesis of the Pittsburg compound-B using a commercial synthesizer.

Verdurand M ，Bort G ，Tadino V ，Bonnefoi F ，Le Bars D ，Zimmer L ... -  《NUCLEAR MEDICINE COMMUNICATIONS》