Microwave-assisted radiosynthesis of [18F]fluorinated fatty acid analogs

Abstract

Microwave reactors remain largely underutilized in the field of positron emission tomography (PET) chemistry. This is particularly unfortunate since microwave synthesis elegantly addresses two of the most critical issues of PET radiochemistry with short-lived radionuclides: reaction rate and side-product formation. In this study, we investigate the efficiency of synthesis of terminally [(18)F]fluorinated fatty acid analogs using a commercial microwave reactor in comparison with conventional heating (CH). The labeling precursors were methyl esters of terminally substituted alkyl bromides and iodides. Duration and temperatures of the [(18)F]fluorination reaction were varied. Chemical and radiochemical purities, and radiochemical yields were investigated for conventional (CH) and microwave-assisted (MW) radiosyntheses. The results demonstrate that microwave heating enhanced [(18)F]fluoride incorporation to >95% (up to 55% improvement), while reducing reaction times to 2 min (∼ 10-fold reduction) or temperatures to 55-60 °C (20 °C reduction). Overall decay-corrected radiochemical yields of purified [(18)F]fluoro fatty acids were higher (MW = 49.0 ± 4.5%, CH = 23.6 ± 3.5%, P < .05) with microwave heating and side-products were notably fewer. For routine synthesis of [(18)F]fluoro fatty acid analogs, microwave heating is faster, milder, cleaner, less variable and higher yielding than CH and therefore the preferred reaction method.