4.3 Article

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

Journal

EJNMMI RESEARCH
Volume 1, Issue -, Pages -

Publisher

SPRINGER
DOI: 10.1186/2191-219X-1-10

Keywords

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

Funding

  1. Academy of Finland [119048]
  2. University of Turku
  3. Turku University Hospital
  4. Turku University Hospital (EVO grant)
  5. Drug Discovery Graduate School
  6. Abo Akademi University

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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.

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