Synthesis of fatty acids specifically labelled with 11C in various positions, including 2H substitution, for in vivo studies of myocardium using PET

Abstract

Fatty acids were labelled with 11C in several positions by reacting [ 11C]carbon dioxide with the appropriate Grignard reagent or by reacting a α,ω-bis-(bromo magnesium) alkane with a 11C-labelled alkyl iodide followed by a reaction with carbon dioxide. The methyl and methylene 11C-labelled fatty acids were obtained in 12–36% (decay corrected) radiochemical yield within 45–65 min, and with radiochemical purities higher than 96%. Perdeuterated α,ω-dibromo hexane, decane and tetradecane were synthesized from dimethylacetylene dicarboxylate by means of a Raney-nickel reduction in D 2O, Kolbe electrolysis and LAD reduction. The use of multiple isotopic labelling by the combination of position specific 11C labelling and 2H substitution, has the potential to highlight different aspects of a complex biochemical system by PET. This principle is illustrated by results of the kinetics of different types of 11C label of dodecanoic acid and the corresponding moieties of acetate. The combination of tracers allows the kinetics of β-oxidation of middle length carbon chain fatty acids and citric acid cycle metabolism to be separately assured, whilst deuteration of the tracers opens the possibility of highlighting the kinetics of the proton extraction processes reflecting rate limiting steps.