Hyper‐Intense Tumor Peripheral Accumulation of Antibody‐Conjugated Iron Oxide Nanoparticles can Enable Breast Cancer Detection by Magnetic Particle Imaging
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
ABSTRACT Targeting nanoparticles to cancer cells in vivo remains a challenge for cancer imaging. We assessed nanoparticle distribution after injecting iron oxide nanoparticles conjugated with either a monoclonal anti‐HER2 (human epidermal growth factor 2), or a non‐specific IgG antibody into a human HER2 overexpressing murine breast cancer model. We used Magnetic Particle Imaging (MPI) and histopathology to assess particle localization at 72 h after injection. MPI detects magnetic moments produced by magnetic particles, and histology enables spatial quantification of nanoparticles. Intratumor iron content measured by MPI correlated with inductively coupled plasma mass spectrometry (= 0.868,< 0.0001). We detected nanoparticle accumulation in tumors, and organs and tissues associated with inflammation. MPI showed higher uptake of nanoparticles in tumors, regardless of their performance in vitro. Spatial analysis showed that 43 ± 7% of nanoparticles that reached the tumor accumulated in the peripheral quartile of the tumor, with decreasing amounts toward the center. Immunohistochemical analysis showed the nanoparticles were strongly associated with inflammatory immune and stromal cells in the tumor microenvironment. This hyperintense peripheral accumulation, or ring pattern, observed with MPI enabled us to distinguish tumors from general inflammation. Iron oxide nanoparticle‐mediated MPI has the potential to detect tumors, providing another powerful diagnostic tool. Tumor‐associ
Abstract
ABSTRACT Targeting nanoparticles to cancer cells in vivo remains a challenge for cancer imaging. We assessed nanoparticle distribution after injecting iron oxide nanoparticles conjugated with either a monoclonal anti‐HER2 (human epidermal growth factor 2), or a non‐specific IgG antibody into a human HER2 overexpressing murine breast cancer model. We used Magnetic Particle Imaging (MPI) and histopathology to assess particle localization at 72 h after injection. MPI detects magnetic moments produced by magnetic particles, and histology enables spatial quantification of nanoparticles. Intratumor iron content measured by MPI correlated with inductively coupled plasma mass spectrometry (= 0.868,< 0.0001). We detected nanoparticle accumulation in tumors, and organs and tissues associated with inflammation. MPI showed higher uptake of nanoparticles in tumors, regardless of their performance in vitro. Spatial analysis showed that 43 ± 7% of nanoparticles that reached the tumor accumulated in the peripheral quartile of the tumor, with decreasing amounts toward the center. Immunohistochemical analysis showed the nanoparticles were strongly associated with inflammatory immune and stromal cells in the tumor microenvironment. This hyperintense peripheral accumulation, or ring pattern, observed with MPI enabled us to distinguish tumors from general inflammation. Iron oxide nanoparticle‐mediated MPI has the potential to detect tumors, providing another powerful diagnostic tool. Tumor‐associated inflammation retains antibody‐targeted or non‐specific antibody conjugated nanoparticles within the tumor microenvironment. Magnetic Particle Imaging (MPI) enables non‐invasive detection and differentiation of tumors from other organs, owing to higher nanoparticle retention by inflammatory cells in the tumor periphery. advs77425-abs-0001 graphical