Details

Autor(en) / Beteiligte

• Qu, Wenchao
• Kothari, Paresh
• waterhouse, Nicole
• Dooley, Marybeth
• Nikolopoulou, Anastasia
• Babich, John

Titel

An Improved Synthesis of Carbon-11 Labeled Arachidonic Acid

Ist Teil von

• The Journal of nuclear medicine (1978), 2018-05, Vol.59, p.1052

Ort / Verlag

New York: Society of Nuclear Medicine

Erscheinungsjahr

2018

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Objectives: As an essential polyunsaturated fatty acid, arachidonic acid (AA) is a second messenger in the phospholipase A2 (PLA2) neural signaling system. Carbon-11 labelled AA ([11C]AA) was developed over two decades ago as a neurological imaging agent. Current method for synthesis of this clinically important PET tracer involves a Grignard reagent/11C-carboxylation synthesis methodology. Due to the lability of the tetraene skeleton of the bromide precursor, the inertness of carbon-bromide bond towards metal insertion and the unstability of newly formed Grignard reagent along with the short half-life of carbon-11 (T1/2 = 20.4 min), the production of [11C]AA for clinical studies is highly challenging. Herein, we describe an improved synthetic procedure for [11C]AA that leads to a more efficient, facile and reliable production of this radiotracer for clinical research purposes. Methods: To ensure the fast and reliable formation of Grignard reagent, several methods were tested, such as the use of highly reactive Rieke® Mg reagent, the addition of isopropyl magnesium chloride for activation and the use of dual-solvents for Grignard reaction. In addition, the volume and the concentration of Grignard reagent during the 11C-carboxylation reaction have been evaluated while a HPLC based purification method have been tested. Results: The simple change from Et2O to Et2O/THF dual solvent system dramatically promoted the rapid formation of the Grignard reagent that was completed in 1 h with mechanic stirring and mild reflux. This reagent efficiently trapped >95% of [11C]CO2 radioactivity affording the [11C]AA product in 70% yields (decay-corrected) and > 92% radiochemical purity with the overall synthetic procedure not exceeding 25 min. Conclusions: A modified synthetic method for the neuroimaging tracer [11C]AA, featuring fast and easy (no extra precautions) preparation of Grignard reagent, has been developed. The freshly formed Grignard reagent results in excellent [11C]CO2 trapping and radiolabeling efficiency. Further work will focus on the development of a EtOH/H2O solvent based HPLC purification method to avoid the use of large amounts of pyrophoric solvent Et2O currently employed in the clinical production of [11C]AA.