Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis

Vascular adhesion protein-1 (VAP-1) is an infection/inflammation-inducible endothelial glycoprotein. Based on our previous studies, the most VAP-1-selective peptide (VAP-P1) was 1,4,7,10-tetraazacyclododecane- N′, N″, N‴, N⁗-tetraacetic acid (DOTA)-conjugated, 68gallium ( 68Ga)-labeled (named [ 68Ga]DOTAVAP-P1) and evaluated preliminarily. Targeting was evaluated by using VAP-1-transfected cells. Biodistribution of [ 68Ga]DOTAVAP-P1 was studied by positron emission tomography imaging of healthy rats and rats with bone inflammation caused by Staphylococcus aureus infection. Uptake of [ 68Ga]DOTAVAP-P1 in osteomyelitis was compared with negative control peptide and competition with an excess of unlabeled DOTAVAP-P1. [ 68Ga]DOTAVAP-P1 bound more efficiently to VAP-1-transfected cells than to controls. In rats, [ 68Ga]DOTAVAP-P1 cleared rapidly from blood circulation, excreted quickly in urine and showed an in vivo half-life of 26±2.3 min. Imaging of osteomyelitis demonstrated modest target-to-background ratio. Studies with the negative control peptide and competitors revealed a significantly lower uptake at the infection site compared to [ 68Ga]DOTAVAP-P1. The results represent a proof-of-concept that infection-induced VAP-1 can be targeted by [ 68Ga]DOTA peptide. [ 68Ga]DOTAVAP-P1 is just the first candidate peptide and an essential opening for developing VAP-1-specific imaging agents.