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



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.



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.



The 25% (64)Cu-CANF-comb demonstrated its potential as a PET imaging agent to detect atherosclerosis progression and status.
Department of Radiology, Washington University, St. Louis, Missouri, USA.
Pamela K
PK
Woodard
Department of Radiology, Washington University, St. Louis, Missouri, USA.
Yongjian
Y
Liu
Materials Research Laboratory, University of California, Santa Barbara, California,, USA.
Eric D
ED
Pressly
Department of Radiology, Washington University, St. Louis, Missouri, USA.
Hannah P
HP
Luehmann
Department of Radiology, Washington University, St. Louis, Missouri, USA.
Lisa
L
Detering
Department of Radiology, Washington University, St. Louis, Missouri, USA.
Deborah E
DE
Sultan
Department of Radiology, Washington University, St. Louis, Missouri, USA.
Richard
R
Laforest
Materials Research Laboratory, University of California, Santa Barbara, California,, USA.
Alaina J
AJ
McGrath
Department of Radiology, Washington University, St. Louis, Missouri, USA.
Robert J
RJ
Gropler
Materials Research Laboratory, University of California, Santa Barbara, California,, USA. hawker@mrl.ucsb.edu.|Department of Chemistry and Biochemistry, University of California, Santa Barbara, California,, USA. hawker@mrl.ucsb.edu.|Materials Department, University of California, Santa Barbara, California, USA. hawker@mrl.ucsb.edu.
Craig J
CJ
Hawker
D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D003301:Copper Radioisotopes; D011108:Polymers; D009320:Atrial Natriuretic Factor
atherosclerosis; nanoparticle; natriuretic peptide clearance receptor; polymer synthesis; positron emission tomography