Preliminary investigation of 11C-AG957 - tyrosine kinase inhibitor as a clinical radiopharmaceutical

Full text: The Philadelphia chromosome fusion of BCR gene on chromosome 22 with c-ABL translocated from chromosome 9 is the hallmark of chronic myelogenous leukaemia (CML). The expression of tyrosine kinase p210 (BCR/ABL) is the result of this translocation. AG957 exert selective inhibition of p210 (BCR/ABL) tyrosine phosphorylation, which can potentially be useful in the management of CML either as a diagnostic indicator or as a tumour targeting agent for therapy. Our centre has successfully labelled AG957 with UC (T 1/2 = 20 minutes) a positron emitting isotope. The procedure involve the labelling of 4-amino benzoic acid with 11C-CH3I, then reacting the HC-methyl ester with 2,5 dihydroxybenzaldehyde and finally reducing the imine using NaCNBHB. Preliminary data show the three step labelling procedure achieves good yield, however, UC-AG957 is highly susceptible to oxidation in solution form. This paper reports the HPLC technique for the determination of radiochemical and chemical purity of UC-AG957. The stability as an injectable was investigated and appropriate conditions were selected to minimise the oxidative process. Preliminary data on the specific activity and overall yield indicate 11C-AG957 is suitable for animal studies. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc