F-18 LABELING OF MONOCLONAL-ANTIBODIES AND FRAGMENTS WITH PRESERVATION OF IMMUNOREACTIVITY

A new method is reported for labeling proteins with the positron-emitting nuclide F-18. Initially, 4-[F-18]-fluorobenzylamine was prepared in two steps from aqueous [F-18]fluoride in high yield. The F-18 acylation agent was formed by reaction of this product with disuccinimidyl suberate. Overall yields for the 4-[F-18]fluorobenzylamine succinimidyl ester ([F-18]SFBS), decay corrected to the end of cyclotron bombardment, were about 30% in a synthesis time of 60 min. After a 15-min reaction, 30-45% (decay corrected) of the [F-18]SFBS could be coupled to intact antibodies and their F(ab')2 and Fab fragments. Coupling yields were dependent on protein concentration but not reaction time. HPLC purification of [F-18]SFBS was necessary to obtain optimal coupling efficiency and immunoreactivity. The immunoreactivities of F-18-labeled F(ab')2 and Fab fragments of an antimyosin antibody were 89 +/- 5% and 75 +/- 9%, respectively. Biodistribution studies in normal mice demonstrated similar in vivo behavior of F-18-labeled antibody fragments and those labeled with I-125 by using N-succinimidyl 3-[I-125]iodobenzoate. These results indicate that this method may be useful for labeling monoclonal antibodies and other proteins and peptides with F-18.