期刊
NUCLEAR MEDICINE AND BIOLOGY
卷 36, 期 6, 页码 631-641出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.nucmedbio.2009.04.008
关键词
(68)Gallium; Positron emission tomography; Experimental osteomyelitis; Vascular adhesion protein-1; DOTA peptide; Infection
资金
- Academy of Finland, University of Turku, Turku University Hospital
- Abo Academy University (Turku, Finland) [205757, 103032]
- Instrumentarium Foundation, the Finnish Cultural Foundation
- Walter and Lisi Wahl Foundation
- Finnish Cultural Foundation
- Eli Lilly Foundation
- Turku University Foundation
- Drug Discovery Graduate School of the University of Turku
- Finnish Graduate School for Musculoskeletal Diseases
- Academy of Finland (AKA) [205757, 103032, 205757, 103032] Funding Source: Academy of Finland (AKA)
Introduction: 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, (68)gallium (Ga-68)-labeled (named [Ga-68]DOTAVAP-P1) and evaluated preliminarily. Methods. Targeting was evaluated by using VAP-1-transfected cells. Biodistribution of [Ga-68]DOTAVAP-P1 was studied by positron emission tomography imaging of healthy rats and rats with bone inflammation caused by Staphylococcus aureus infection. Uptake of [Ga-68] DOTAVAP-P1 in osteomyelitis was compared with negative control peptide and competition with an excess of unlabeled DOTAVAP-P1. Results: [Ga-68]DOTAVAP-P1 bound more efficiently to VAP-1-transfected cells than to controls. In rats, [Ga-68]DOTAVAP-P1 cleared rapidly front 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 [Ga-68]DOTAVAP-P1. Conclusions: The results represent a proof-of-concept that infection-induced VAP-1 can be targeted by [Ga-68]DOTA peptide. [Ga-68] DOTAVAP-P1 is just the first candidate peptide and an essential opening for developing VAP-1-specific imaging agents. (C) 2009 Elsevier Inc. All rights reserved.
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