ImmunoPET imaging of pancreatic tumors with (89)Zr-labeled gold nanoparticle-antibody conjugates Journal Article

Authors: Sobol, N. B.; Korsen, J. A.; Younes, A.; Edwards, K. J.; Lewis, J. S.
Article Title: ImmunoPET imaging of pancreatic tumors with (89)Zr-labeled gold nanoparticle-antibody conjugates
Abstract: Purpose: Targeted delivery in vivo remains an immense roadblock for the translation of nanomaterials into the clinic. The greatest obstacle is the mononuclear phagocyte system (MPS), which sequesters foreign substances from general circulation and causes accumulation in organs such as the liver and spleen. The purpose of this study was to determine whether attaching an active targeting antibody, 5B1, to the surface of gold nanoparticles and using clodronate liposomes to deplete liver and splenic macrophages could help to minimize uptake by MPS organs, increase targeted delivery to CA19.9-positive pancreatic tumors, and enhance pancreatic tumor delineation. Procedures: To produce the antibody-gold nanoparticle conjugate (Ab-AuNP), the Ab was conjugated to p-isothiocyanatobenzyl-desferrioxamine (p-SCN-DFO) and subsequently conjugated to NHS-activated gold nanoparticles. The Ab-AuNP was characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Modified Lindmo assay was performed to assess binding affinity and internalization potential in vitro. The Ab-AuNP was radiolabeled with 89Zr and injected into CA19.9-positive BxPc-3 pancreatic orthotopic tumor-bearing mice pretreated with or without clodronate liposomes for PET imaging and biodistribution studies. Inductively coupled plasma-optical emission spectrometry (ICP-OES) analysis was used to confirm delivery of gold nanoparticles to BxPc-3 pancreatic subcutaneous xenografts. Results: Mice pretreated with clodronate liposomes in an orthotopic setting demonstrated decreased liver uptake at early time points (12.2 ± 2.3 % ID/g vs. 22.8 ± 3.8 % ID/g at 24 h) and increased tumor uptake at 120 h (13.8 ± 8.0 % ID/g vs. 6.0 ± 1.2 % ID/g). This allowed for delineation of orthotopic pancreatic xenografts in significantly more mice treated with clodronate (6/6) than in mice not treated with clodronate (2/6) or mice injected with gold nanoparticles labeled with a nonspecific antibody (0/5). Conclusions: The combination of clodronate liposomes and an active targeting antibody on the surface of gold nanoparticles allowed for PET/CT imaging of subcutaneous and orthotopic pancreatic xenografts in mice. © 2020, World Molecular Imaging Society.
Keywords: controlled study; unclassified drug; liver function; nonhuman; positron emission tomography; binding affinity; mouse; animal tissue; ca 19-9 antigen; animal experiment; animal model; in vitro study; tumor xenograft; molecular imaging; assay; pancreas tumor; antibody specificity; kupffer cell; pancreatic cancer; povidone iodine; bupivacaine; spectroscopy; zirconium-89; zirconium 89; deferoxamine; liposome; drug delivery system; human monoclonal antibody; pet/ct imaging; transmission electron microscopy; meloxicam; clodronic acid; buprenorphine; atomic force microscopy; gold nanoparticles; gold nanoparticle; radiolabeling; female; priority journal; article; clodronate liposomes; antibody drug conjugate; radiolabeled antibody; bxpc-3 cell line; antibody-labeled nanoparticles; 5b1 monoclonal antibody; para isothiocyanatobenzyl desferrioxamine; inductively coupled plasma optical emission spectrometry; internalization (cell); modified lindmo assay; spleen function
Journal Title: Molecular Imaging and Biology
Volume: 23
Issue: 1
ISSN: 1536-1632
Publisher: Springer  
Date Published: 2021-02-01
Start Page: 84
End Page: 94
Language: English
DOI: 10.1007/s11307-020-01535-3
PUBMED: 32909244
PROVIDER: scopus
PMCID: PMC7785666
Notes: Article -- Export Date: 1 February 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Jason S Lewis
    377 Lewis
  2. Kimberly Joanna Edwards
    17 Edwards
  3. Nicholas Sobol
    7 Sobol
  4. Joshua Aaron Korsen
    7 Korsen