A new approach for the synthesis of [11C]-labeled fatty acids

The synthesis of ω-[11C], ω-1-[11C] and ω-3-[11C] palmitic acid employing a cross-coupling reaction between a functionalized copper-zinc reagent with [11C]MeI, [1-11C]EtI and [1-11C]BuI is described. A tert-butyl-protected ω-iodo fatty acid precursor tBuO2C-(CH2)n-I (n = 11, 13, 14) was converted into the corresponding dialkylzinc reagent [tBuO2C-(CH2)n]2Zn which reacts with Me2CuI(MgCl)2 to give a highly reactive copper reagent [tBuO2C-(CH2)n]2CuI(MgCl)2 Me2Zn as the labeling precursor. The cross-coupling reaction with [11C]MeI, [1-11C]EtI and [1-11C]BuI provided the protected palmitic acid, specifically labeled with carbon-11 in several positions. The corresponding carbon-13 labeled compounds were synthesized to verify the labeling position. In a typical synthesis with [1-11C]EtI starting with 250 mCi of [11C]CO2, 14 mCi (6% decay-corrected based on [11C]CO2) of ω-1-[11C]palmitic acid was obtained within 30 minutes after EOB in 88% radiochemical purity prior to purification by HPLC. The general feature of this approach allows the convenient synthesis of palmitic acid specifically labeled in the ω, ω-1 or ω-3 positions by using several [11C]-labeled alkyl iodides ([11C]MeI, [1-11C]EtI or [1-11C]BuI) in the same cross-coupling protocol. Copyright © 2000 John Wiley & Sons, Ltd.