Rapid F-18 labeling of peptides using aniline catalyzed oximation with [18F]FDG

1498 Objectives Despite recent advances, F-18 labeling of peptides for PET imaging remains challenging. It involves multiple step synthesis and low overall yield. An oxime formation between an aminoxy derivatized peptide and [18F]fluorodeoxyglucose(FDG) offers a promising approach for peptide labeling. However, this approach is relatively inefficient due to lower reactivity of FDG. We have previously demonstrated that this reaction could be significantly accelerated using nucleophilic iminium catalysis.Similarly, FDG coupling was also significantly accelerated in the presence of aniline with a model substrate O-benzylhydroxylamine (OBzA). We have used this technique to develop methodology to efficiently label a novel peptide,β-endorphin(β-end) with F-18. Methods [19F]FDG and OBzA were used as model compounds to investigate the oxime coupling reaction. Extended incubation of equimolar amounts of [19F]FDG and OBzA yielded corresponding oxime in 39% yield. Similarly, 15 nmol of β-end was incubated with 0.2 μmol of [19F]FDG in 0.2 M amm. acetate or 0.2 M anilinium acetate acetate at 80o for 30 min. HPLC, mass spectrometry and radio-TLC/HPLC were used to confirm the formation of the desired oxime. Subsequently, oximation reaction was performed using [18F]FDG and OBzA or β-end under the similar conditions. Results As expected, in the cold synthesis with [19F]FDG, the oxime formation proceeded to yield the desired product with OBzA and β-end with or without the catalyst (aniline). The labeling efficiency, however, was significantly higher with the catalyst. In the presence of catalyst, with [18F]FDG, the radiolabeling efficiency of OBzA was 50-70% and with β-end was 20-30% respectively. Conclusions These preliminary data clearly demonstrate that oxime formation reaction catalyzed by aniline can be successfully applied for 18F labeling of peptides