Design and Modular Construction of a Polymeric Nanoparticle for Targeted Atherosclerosis Positron Emission Tomography Imaging: A Story of 25% .sup.64Cu-CANF-Comb

Purpose To assess the physicochemical properties, pharmacokinetic profiles, and in vivo positron emission tomography (PET) imaging of natriuretic peptide clearance receptors (NPRC) expressed on atherosclerotic plaque of a series of targeted, polymeric nanoparticles. Methods To control their structur...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutical research 2016-10, Vol.33 (10)
Main Authors: Woodard, Pamela K, Liu, Yongjian, Pressly, Eric D, Luehmann, Hannah P, Detering, Lisa, Sultan, Deborah E, Laforest, Richard
Format: Article
Language:English
Subjects:
Apolipoproteins
Atherosclerosis
Mice
Natriuretic peptides
PET imaging
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Purpose To assess the physicochemical properties, pharmacokinetic profiles, and in vivo positron emission tomography (PET) imaging of natriuretic peptide clearance receptors (NPRC) expressed on atherosclerotic plaque of a series of targeted, polymeric nanoparticles. Methods To control their structure, non-targeted and targeted polymeric (comb) nanoparticles, conjugated with various amounts of c-atrial natriuretic peptide (CANF, 0, 5, 10 and 25%), were synthesized by controlled and modular chemistry. In vivo pharmacokinetic evaluation of these nanoparticles was performed in wildtype (WT) C57BL/6 mice after .sup.64Cu radiolabeling. PET imaging was performed on an apolipoprotein E-deficient (ApoE.sup.-/-) mouse atherosclerosis model to assess the NPRC targeting efficiency. For comparison, an in vivo blood metabolism study was carried out in WT mice. Results All three .sup.64Cu-CANF-comb nanoparticles showed improved biodistribution profiles, including significantly reduced accumulation in both liver and spleen, compared to the non-targeted .sup.64Cu-comb. Of the three nanoparticles, the 25% .sup.64Cu-CANF-comb demonstrated the best NPRC targeting specificity and sensitivity in ApoE.sup.-/- mice. Metabolism studies showed that the radiolabeled CANF-comb was stable in blood up to 9 days. Histopathological analyses confirmed the up-regulation of NPRC along the progression of atherosclerosis. Conclusion The 25% .sup.64Cu-CANF-comb demonstrated its potential as a PET imaging agent to detect atherosclerosis progression and status.
ISSN:0724-8741
DOI:10.1007/s11095-016-1963-8