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

The synthesis of omega-[C-11], omega -1-[C-11] and omega -3-[C-11:] palmiti c acid employing a cross-coupling reaction between a functionalized copper- zinc reagent with [C-11]Mel, [1-C-11]EtI and [1-C-11]BuI is described. A te rt.-butyl-protected omega -iodo fatty acid precursor (BuO2C)-Bu-t-(CH2)n-I (n = 11, 13, 14) was converted into the corresponding dialkylzinc reagent [ (BuO2C)-Bu-t-(CH2)(n)](2)Zn which reacts with Me2CuI(MgCl)(2) to give a hig hly reactive copper reagent [(BuO2C)-Bu-t-(CH2)(N)](2)CuI(MgCl)(2)Me2Zn as the labeling precursor. The cross-coupling reaction with [C-11]MeI, [1-C-11 :]EB and [1-C-11]BuI provided the protected palmitic acid, specifically lab eled with carbon-11 in several positions. The corresponding carbon-13 label ed compounds were synthesized to verify the labeling position. In a typical synthesis with [1-C-11]EtI starting with 250 mCi of [C-11]CO2, 14 mCi (6% decay-corrected based on [C-11]CO2) of omega -1-[C-11]palmitic acid was obt ained within 30 minutes after EOB in 88% radiochemical purity prior to puri fication by HPLC. The general feature of this approach allows the convenien t synthesis of palmitic acid specifically labeled in the omega, omega -1 or omega -3 positions by using several [C-11]-labeled alkyl iodides ([C-11]Me I, [1-C-11]EtI or [1-C-11]BuI) in the same cross-coupling protocol.