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

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.