SYNTHESIS OF [1-C-11], [2-C-11], [1-C-11](H-2(3)) AND [2-C-11](H-2(3))ACETATE FOR IN-VIVO STUDIES OF MYOCARDIUM USING PET

Four isotopically-labelled acetates ([1-C-11], [2-C-11], [1-C-11](H-2(3)) and [2-C-11](H-2(3))acetate) were synthesized and used in positron emission tomography (PET) studies of pig myocardium. The [1-C-11]acetates were synthesized by carboxylation of the appropriate H-1 or H-2 methyl Grignard reagents immobilized on a C-2 solid phase extraction column (SPE). Purification by reverse-phase HPLC, resulted in 35-45% decay-corrected radiochemical yield with a total synthesis time of 25 min, and a radiochemical purity higher than 99%. The [2-C-11]acetates were synthesized by carboxylation of C-11-labelled H-1 or H-2 methyl lithium. Purification as above resulted in 35-55% decay-corrected radiochemical yield with a total synthesis time of 30 min, and a radiochemical purity higher than 99%. Position-specific labelling was assessed by C-13-labelling and NMR. Multiple isotopic labelling by the combination of position-specific C-11-labelling and H-2 substitution, has the potential to highlight different aspects of a complex biochemical system using a selected set of tracers in comparative PET studies. An illustration of this principle is given using acetate, where citric acid cycle metabolism results in a position-specific kinetic for the C-11-label, and deuteration opens up the possibility for the proton-abstracting processes within the citric acid cycle to be assessed.