Back to Search
Start Over
Mini-PEG spacering of VAP-1-targeting 68Ga-DOTAVAP-P1 peptide improves PET imaging of inflammation
- Source :
- EJNMMI Research
- Publisher :
- Springer Nature
-
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 0.33 ± 0.07 for 68Ga-DOTAVAP-P1 and 0.53 ± 0.01 for 68Ga-DOTAVAP-PEG-P1 by PET. In addition, inflammation-to-muscle ratios were 6.7 ± 1.3 and 7.3 ± 2.1 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 spacer prolonged the metabolic half-life of the 68Ga-DOTAVAP-P1 peptide, leading to higher target-to-background ratios and improved in vivo PET imaging of inflammation.
- Subjects :
- mini-PEG spacer
Pathology
medicine.medical_specialty
positron emission tomography
Inflammation
Peptide
Pharmacology
030218 nuclear medicine & medical imaging
03 medical and health sciences
0302 clinical medicine
gallium-68
In vivo
PEG ratio
medicine
Radiology, Nuclear Medicine and imaging
Original Research
chemistry.chemical_classification
business.industry
vascular adhesion protein-1
inflammation imaging
Imaging agent
chemistry
030220 oncology & carcinogenesis
Renal physiology
medicine.symptom
business
Ex vivo
Preclinical imaging
Subjects
Details
- Language :
- English
- ISSN :
- 2191219X
- Volume :
- 1
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- EJNMMI Research
- Accession number :
- edsair.doi.dedup.....f495571f9f3f3526738821e29a68d55e
- Full Text :
- https://doi.org/10.1186/2191-219x-1-10