Pamela K Woodard1, Yongjian Liu1, Eric D Pressly2, Hannah P Luehmann1, Lisa Detering1, Deborah E Sultan1, Richard Laforest1, Alaina J McGrath2, Robert J Gropler1, Craig J Hawker3,4,5. 1. Department of Radiology, Washington University, St. Louis, Missouri, USA. 2. Materials Research Laboratory, University of California, Santa Barbara, California,, USA. 3. Materials Research Laboratory, University of California, Santa Barbara, California,, USA. hawker@mrl.ucsb.edu. 4. Department of Chemistry and Biochemistry, University of California, Santa Barbara, California,, USA. hawker@mrl.ucsb.edu. 5. Materials Department, University of California, Santa Barbara, California, USA. hawker@mrl.ucsb.edu.
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 (64)Cu 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 (64)Cu-CANF-comb nanoparticles showed improved biodistribution profiles, including significantly reduced accumulation in both liver and spleen, compared to the non-targeted (64)Cu-comb. Of the three nanoparticles, the 25% (64)Cu-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% (64)Cu-CANF-comb demonstrated its potential as a PET imaging agent to detect atherosclerosis progression and status.
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 (64)Cu radiolabeling. PET imaging was performed on an apolipoprotein E-deficient (ApoE(-/-)) mouseatherosclerosis model to assess the NPRC targeting efficiency. For comparison, an in vivo blood metabolism study was carried out in WT mice. RESULTS: All three (64)Cu-CANF-comb nanoparticles showed improved biodistribution profiles, including significantly reduced accumulation in both liver and spleen, compared to the non-targeted (64)Cu-comb. Of the three nanoparticles, the 25% (64)Cu-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% (64)Cu-CANF-comb demonstrated its potential as a PET imaging agent to detect atherosclerosis progression and status.
Authors: Victor H Casco; John P Veinot; Mercedes L Kuroski de Bold; Roy G Masters; Michelle M Stevenson; Adolfo J de Bold Journal: J Histochem Cytochem Date: 2002-06 Impact factor: 2.479
Authors: Agnese Irkle; Alex T Vesey; David Y Lewis; Jeremy N Skepper; Joseph L E Bird; Marc R Dweck; Francis R Joshi; Ferdia A Gallagher; Elizabeth A Warburton; Martin R Bennett; Kevin M Brindle; David E Newby; James H Rudd; Anthony P Davenport Journal: Nat Commun Date: 2015-07-07 Impact factor: 14.919
Authors: Antonio Maria Sammartino; Raffaele Falco; Andrea Drera; Francesco Dondi; Pietro Bellini; Francesco Bertagna; Enrico Vizzardi Journal: Int J Cardiovasc Imaging Date: 2022-10-18 Impact factor: 2.316
Authors: Shentian Wu; Edward Helal-Neto; Ana Paula Dos Santos Matos; Amir Jafari; Ján Kozempel; Yuri José de Albuquerque Silva; Carolina Serrano-Larrea; Severino Alves Junior; Eduardo Ricci-Junior; Frank Alexis; Ralph Santos-Oliveira Journal: Drug Deliv Date: 2020-12 Impact factor: 6.419