In vivo tumor vasculature targeted PET/NIRF imaging with TRC105(Fab)-conjugated, dual-labeled mesoporous silica nanoparticles

Mol Pharm. 2014 Nov 3;11(11):4007-14. doi: 10.1021/mp500306k. Epub 2014 Jun 25.

Abstract

Multifunctional mesoporous silica nanoparticles (MSN) with well-integrated multimodality imaging properties have generated increasing research interest in the past decade. However, limited progress has been made in developing MSN-based multimodality imaging agents to image tumors. We describe the successful conjugation of, copper-64 ((64)Cu, t1/2 = 12.7 h), 800CW (a near-infrared fluorescence [NIRF] dye), and TRC105 (a human/murine chimeric IgG1 monoclonal antibody) to the surface of MSN via well-developed surface engineering procedures, resulting in a dual-labeled MSN for in vivo targeted positron emission tomography (PET) imaging/NIRF imaging of the tumor vasculature. Pharmacokinetics and tumor targeting efficacy/specificity in 4T1 murine breast tumor-bearing mice were thoroughly investigated through various in vitro, in vivo, and ex vivo experiments. Dual-labeled MSN is an attractive candidate for future cancer theranostics.

Keywords: mesoporous silica nanoparticle (MSN); near-infrared fluorescence (NIRF) imaging; positron emission tomography (PET) imaging; vasculature targeting.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / chemistry
  • Antibodies, Monoclonal* / pharmacokinetics
  • Copper Radioisotopes / pharmacokinetics
  • Female
  • Fluorescence
  • Immunoglobulin G / immunology
  • Mammary Neoplasms, Animal / diagnostic imaging*
  • Mammary Neoplasms, Animal / immunology
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Mice, Inbred BALB C
  • Multimodal Imaging
  • Nanoparticles / chemistry*
  • Neovascularization, Pathologic / diagnostic imaging*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals* / pharmacokinetics
  • Silicon Dioxide / chemistry*
  • Spectroscopy, Near-Infrared
  • Tissue Distribution
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Copper Radioisotopes
  • Immunoglobulin G
  • Radiopharmaceuticals
  • Silicon Dioxide
  • carotuximab