Preliminary evaluation of novel 68Ga-DOTAVAP-PEG-P2 peptide targeting vascular adhesion protein-1

Expression of vascular adhesion protein-1 (VAP-1) is induced at the sites of inflammation where extravasation of leukocytes from blood to the peripheral tissue occurs. VAP-1 is a potential target for anti-inflammatory therapy and for in vivo imaging of inflammation. Purpose of this study was to preliminarily evaluate a novel VAP-1-targeting peptide as a potential PET imaging agent.

Cyclic 17-amino-acid peptide selected from phage display libraries was 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) conjugated via 8-amino-3,6-diooxaoctanoyl linker (polyethylene glycol, PEG derivative) and labelled with (68)Ga ((68)Ga-DOTAVAP-PEG-P2). In vitro stability of (68)Ga-DOTAVAP-PEG-P2 was determined in saline, rat plasma and human plasma by radio-HLPC. Lipophilicity was measured by calculating octanol-water partition coefficient (logP). Whole-body distribution kinetics and stability after intravenous injection in healthy rats was studied in vivo by PET imaging, ex vivo by measuring radioactivity of excised tissues, and by radio-HPLC.

In vitro the (68)Ga-DOTAVAP-PEG-P2 remained stable >4 h in saline and rat plasma, but degraded slowly in human plasma after 2 h of incubation. The logP value of (68)Ga-DOTAVAP-PEG-P2 was -1.3. In rats, (68)Ga-radioactivity cleared rapidly from blood circulation and excreted quickly in urine. At 120 min after injection the fraction of intact (68)Ga-DOTAVAP-PEG-P2 were 77 +/- 6.0% and 99 +/- 1.0% in rat plasma and urine, respectively.

These basic and essential in vitro and in vivo studies of the new VAP-1 targeting peptide revealed promising properties for an imaging agent. Further investigations to clarify in vivo VAP-1 targeting are warranted.