TAILIEUCHUNG - Autio et al. EJNMMI Research 2011, 1:10 http://www.ejnmmires.com/content/1/1/10 ORIGINAL

Autio et al. EJNMMI Research 2011, 1:10 ORIGINAL RESEARCH Open Access Mini-PEG spacering of VAP-1-targeting 68 Ga-DOTAVAP-P1 peptide improves PET imaging of inflammation Anu Autio1, Tiina Henttinen2, Henri J Sipilä1, Sirpa Jalkanen3 and Anne Roivainen1,4* Abstract Background: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule that plays a key role in recruiting leucocytes into sites of inflammation. We have previously shown that 68Gallium-labelled VAP-1-targeting peptide (68Ga-DOTAVAP-P1) is a positron emission tomography (PET) imaging agent, capable of visualising inflammation in rats, but disadvantaged by its short metabolic half-life and rapid clearance. We hypothesised that prolonging the metabolic half-life of 68Ga-DOTAVAP-P1 could further improve its imaging characteristics | Autio et al. EJNMMI Research 2011 1 10 http content 1 1 10 9 EJNMMI Research a SpringerOpen Journal ORIGINAL RESEARCH Open Access Mini-PEG spacering of VAP-1-targeting 68Ga-DOTAVAP-P1 peptide improves PET imaging of inflammation Anu Autio1 Tiina Henttinen2 Henri J Sipila1 Sirpa Jalkanen3 and Anne Roivainen1 4 Abstract Background Vascular adhesion protein-1 VAP-1 is an adhesion molecule that plays a key role in recruiting leucocytes into sites of inflammation. We have previously shown that 68Gallium-labelled VAP-1-targeting peptide 68Ga-DOTAVAP-P1 is a positron emission tomography PET imaging agent capable of visualising inflammation in rats but disadvantaged by its short metabolic half-life and rapid clearance. We hypothesised that prolonging the metabolic half-life of 68Ga-DOTAVAP-P1 could further improve its imaging characteristics. In this study we evaluated a new analogue of 68Ga-DOTAVAP-P1 modified with a mini-polyethylene glycol PEG spacer 68Ga-DOTAVAP-PEG-P1 for in vivo imaging of inflammation. Methods Whole-body distribution kinetics and visualisation of inflammation in a rat model by the peptides 68Ga-DOTAVAP-P1 and 68Ga-DOTAVAP-PEG-P1 were evaluated in vivo by dynamic PET imaging and ex vivo by measuring the radioactivity of excised tissues. In addition plasma samples were analysed by radio-HPLC for the in vivo stability of the peptides. Results The peptide with the mini-PEG spacer showed slower renal excretion but similar liver uptake as the original peptide. At 60 min after injection the standardised uptake value of the inflammation site was for 68Ga-DOTAVAP-P1 and for 68Ga-DOTAVAP-PEG-P1 by PET. In addition inflammation-to-muscle ratios were and for 68Ga-DOTAVAP-P1 and 68Ga-DOTAVAP-PEG-P1 respectively. The proportion of unchanged peptide in circulation at 60 min after injection was significantly higher for 68Ga-DOTAVAP-PEG-P1 76 than for 68Ga-DOTAVAP-P1 19 . Conclusion The eight-carbon mini-PEG .

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