Biodistribution and catabolism of 18F-labelled isopeptide Nɛ-(γ-glutamyl)-L-lysine

Isopeptide bonds between the ɛ-amino group of lysine and the γ-carboxamide group of glutamine are formed during strong heating of pure proteins or, more important, by enzymatic reaction mediated by transglutaminases. Despite the wide use of a microbial transglutaminase in food biotechnology, up to now little is known about the metabolic fate of the isopeptide Nɛ-(γ-glutamyl)-L-lysine. In the present study, N-succinimidyl-4-[18F]fluorobenzoate was used to modify Nɛ-(γ-glutamyl)-L-lysine at each of its two α-amino groups, resulting in the 4-[18F]fluorobenzoylated derivatives, for which biodistribution, catabolism, and elimination were investigated in male Wistar rats. A significant different biochemical behavior of the two labelled isopeptides was observed in terms of in vitro stability, in vivo metabolism as well as biodistribution. The results suggest that the metabolic fate of isopeptides is likely to be dependent on how they are reabsorbed – free or peptide bound.