Fully automated synthesis of ¹¹C-acetate as tumor PET tracer by simple modified solid-phase extraction purification.

Automated synthesis of (11)C-acetate ((11)C-AC) as the most commonly used radioactive fatty acid tracer is performed by a simple, rapid, and modified solid-phase extraction (SPE) purification. Automated synthesis of (11)C-AC was implemented by carboxylation reaction of MeMgBr on a polyethylene Teflon loop ring with (11)C-CO2, followed by acidic hydrolysis with acid and SCX cartridge, and purification on SCX, AG11A8 and C18 SPE cartridges using a commercially available (11)C-tracer synthesizer. Quality control test and animals positron emission tomography (PET) imaging were also carried out. A high and reproducible decay-uncorrected radiochemical yield of (41.0 ± 4.6)% (n=10) was obtained from (11)C-CO2 within the whole synthesis time about 8 min. The radiochemical purity of (11)C-AC was over 95% by high-performance liquid chromatography (HPLC) analysis. Quality control test and PET imaging showed that (11)C-AC injection produced by the simple SPE procedure was safe and efficient, and was in agreement with the current Chinese radiopharmaceutical quality control guidelines. The novel, simple, and rapid method is readily adapted to the fully automated synthesis of (11)C-AC on several existing commercial synthesis module. The method can be used routinely to produce (11)C-AC for preclinical and clinical studies with PET imaging.

Tang X ，Tang G ，Nie D 《-》

An automated SPE-based high-yield synthesis of [11C]acetate and [11C]palmitate: no liquid-liquid extraction, solvent evaporation or distillation required.

An automated method is described for the rapid and high-yield synthesis of two of the most commonly used radioactive fatty acids: [(11)C]acetate and [(11)C]palmitate. Reaction of [(11)C]CO(2) with the respective Grignard reagents in diethyl ether solution proceeded for 2 min at 40°C. Quenching of the reaction and liberation of nonreacted [(11)C]CO(2) occurred upon addition of a fourfold molar excess of aqueous 0.1 M HCl (acetate) or nonaqueous HCl/Et(2)O (palmitate). Labeled products were then purified by adsorption to an Alumina-N Sep-Pak Plus cartridge and eluted with either aqueous NaH(2)PO(4) solution (acetate) or 100% ethanol (palmitate). High-performance liquid chromatography analysis confirmed that the radiochemical purity of each product was >98%, and decay-corrected radiochemical yields averaged 33% for [(11)C]palmitate and 40% for [(11)C]acetate. The method requires no liquid-liquid extraction, solvent evaporation or distillation capabilities and can be readily adapted to existing radiosynthesis modules.

Mock BH ，Brown-Proctor C ，Green MA ，Steele B ，Glick-Wilson BE ，Zheng QH ... -  《-》

High-yielding, automated production of 3'-deoxy-3'-[(18)F]fluorothymidine using a modified Bioscan Coincidence FDG reaction module.

High-yielding, automated production of a PET tracer that reflects proliferation, 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), is reported using a modified Bioscan Coincidence FDG reaction module. Production of [(18)F]FLT was implemented through: (1) modification of an original FDG manifold; (2) application of an alternate time sequence; and (3) altered solid-phase extraction (SPE) purification. Quality control testing, including standard radiochemical figures of merit and preclinical positron emission tomography (PET) imaging, was carried out. High decay-corrected yields of [(18)F]FLT (16-39%) were reproducibly obtained. The product exhibited very high specific activity (4586.9TBq/mmol; 123,969Ci/mmol) and radiochemical purity (>99%). Overall, the [(18)F]FLT produced in this manner was superior to typical productions that utilized a GE TRACERlab FXF-N reaction module. Additionally, purification with SPE cartridges, followed by manual elution, accelerated overall run time and resulted in a two-fold increase in [(18)F]FLT concentration. PET imaging showed the [(18)F]FLT produced by this method was highly suitable for non-invasive tumor imaging in mice. The Bioscan Coincidence GE FDG Reaction Module was readily adapted to reproducibly provide [(18)F]FLT in high yield, specific activity, and radiochemical purity. The approach was suitable to provide sufficient amounts of material for preclinical studies.

Cheung YY ，Nickels ML ，McKinley ET ，Buck JR ，Manning HC ... -  《-》

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 《-》

Easy upgrade of the TRACERLab FX C Pro for [¹¹C]carboxylation reactions: application to the routine production of [1-¹¹C]acetate.

Carbon-11-labeled acetate ([1-(11)C]acetate) is a radiopharmaceutical of importance in clinical practice as well as in preclinical research in cardiology and oncology. Its preparation is based on the [(11)C]carboxylation reaction of a Grignard reagent with [(11)C]CO2. Most of the commercially available synthesizers are only dedicated to the preparation of [(11)C]methyl iodide (or [(11)C]methyl triflate) for the radiomethylation of an appropriate precursor but not for the direct use of cyclotron-produced [(11)C]CO2. Based on the classical [(11)C]carboxylation reaction and SPE purification, we propose in this technical note a detailed, simple, easy-to-handle and fully reversible modification of the TRACERLab FX C Pro to operate, on demand, [(11)C]carboxylation reactions, exemplified herein by the production of [1-(11)C]acetate, or [(11)C]radiomethylation reactions. This also opens new prospects to other type of radiochemical reactions involving [(11)C]CO2.

Le Helleix S ，Dollé F ，Kuhnast B 《-》