Mini-PEG spacering of VAP-1-targeting Ga-68-DOTAVAP-P1 peptide improves PET imaging of inflammation

作者：Autio Anu; Henttinen Tiina; Sipila Henri J; Jalkanen Sirpa; Roivainen Anne^*

来源：EJNMMI Research, 2011, 1: 10.

DOI：10.1186/2191-219X-1-10

• gallium-68
• inflammation imaging
• mini-PEG spacer
• positron emission tomography
• vascular adhesion protein-1

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 (68)Gallium-labelled VAP-1-targeting peptide (Ga-68-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 Ga-68-DOTAVAP-P1 could further improve its imaging characteristics. In this study, we evaluated a new analogue of Ga-68-DOTAVAP-P1 modified with a mini-polyethylene glycol (PEG) spacer (Ga-68-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 Ga-68-DOTAVAP-P1 and Ga-68-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 0.33 +/- 0.07 for Ga-68-DOTAVAP-P1 and 0.53 +/- 0.01 for Ga-68-DOTAVAP-PEG-P1 by PET. In addition, inflammation-to-muscle ratios were 6.7 +/- 1.3 and 7.3 +/- 2.1 for Ga-68-DOTAVAP-P1 and Ga-68-DOTAVAP-PEG-P1, respectively. The proportion of unchanged peptide in circulation at 60 min after injection was significantly higher for Ga-68-DOTAVAP-PEG-P1 (76%) than for Ga-68-DOTAVAP-P1 (19%).
Conclusion: The eight-carbon mini-PEG spacer prolonged the metabolic half-life of the Ga-68-DOTAVAP-P1 peptide, leading to higher target-to-background ratios and improved in vivo PET imaging of inflammation.

• 出版日期2011