Automated, Transferable, and Ethanol-Free Radiosynthesis of [11C]Butanol

• Published in: ACS chemical neuroscience Vol. 15; no. 19; pp. 3535 - 3542
• Main Authors: Oyeniran, Olujide, Liu, Linshan, Raymond, Confidence, Moyaert, Paulien, Kovacs, Michael S., Anazodo, Udunna C., Hicks, Justin W.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02.10.2024
• Subjects: Animals; Brain - diagnostic imaging; Butanols - chemical synthesis; Butanols - chemistry; Carbon Radioisotopes; Ethanol - chemistry; Positron-Emission Tomography - methods; Radiopharmaceuticals - chemical synthesis; Swine; cerebral blood flow; automated radiosynthesize; blood–brain barrier; [11C]butanol; PET
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.4c00455

Cerebral blood flow and blood–brain barrier permeability assessment are crucial hemodynamic parameters to measure under neurological conditions. In conjunction with positron emission tomography (PET), oxygen-15-labeled water has emerged as a gold standard for measuring cerebral perfusion; however, at higher flow rates, [15O]­water extraction becomes nonlinear. In such a scenario, freely diffusible [11C]­butanol can provide a truer estimate. Radiosyntheses of [11C]­butanol reported to date are protracted, are not automated, or require ethanol in the final formulation. By using a flow-based, captive solvent approach on a commercially available radiosynthesizer, we automated and reduced the synthesis time to 28 min. Forgoing cartridge-based purification for an aqueous high-performance liquid chromatography method, we obtained high purity [11C]­butanol in ethanol-free phosphate buffered saline in sufficient yields for clinical PET studies. We here report our expedited, automated, and ethanol-free radiosynthesis of [11C]­butanol along with preliminary imaging of a porcine subject.