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

Pamela K. Woodard, Yongjian Liu, Eric D. Pressly, Hannah P. Luehmann, Lisa Detering, Deborah E. Sultan, Richard Laforest, Alaina J. McGrath, Robert J. Gropler, Craig J. Hawker

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 64Cu radiolabeling. PET imaging was performed on an apolipoprotein E–deficient (ApoE−/−) 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 64Cu-CANF-comb nanoparticles showed improved biodistribution profiles, including significantly reduced accumulation in both liver and spleen, compared to the non-targeted 64Cu-comb. Of the three nanoparticles, the 25% 64Cu-CANF-comb demonstrated the best NPRC targeting specificity and sensitivity in ApoE−/− 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% 64Cu-CANF-comb demonstrated its potential as a PET imaging agent to detect atherosclerosis progression and status.

Original languageEnglish
Pages (from-to)2400-2410
Number of pages11
JournalPharmaceutical Research
Volume33
Issue number10
DOIs
StatePublished - Oct 1 2016

Keywords

  • atherosclerosis
  • nanoparticle
  • natriuretic peptide clearance receptor
  • polymer synthesis
  • positron emission tomography

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