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


METHODS
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 [(68)Ga]DOTAVAP-P1 in osteomyelitis was compared with negative control peptide and competition with an excess of unlabeled DOTAVAP-P1.


RESULTS
[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.


CONCLUSIONS
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.
Ujula
Tiina
T
Turku PET Center, Turku University Hospital, Turku, Finland.
Salomäki
Satu
S
Virsu
Pauliina
P
Lankinen
Petteri
P
Mäkinen
Tatu J
TJ
Autio
Anu
A
Yegutkin
Gennady G
GG
Knuuti
Juhani
J
Jalkanen
Sirpa
S
Roivainen
Anne
A
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005710:Gallium Radioisotopes / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010019:Osteomyelitis / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D014018:Tissue Distribution
D015815:Cell Adhesion Molecules; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); C510433:vascular adhesion protein-1, rat