Magnetic Particle Imaging-Guided Heating in Vivo Using Gradient Fields for Arbitrary Localization of Magnetic Hyperthermia Therapy

ACS Nano. 2018 Apr 24;12(4):3699-3713. doi: 10.1021/acsnano.8b00893. Epub 2018 Mar 28.

Abstract

Image-guided treatment of cancer enables physicians to localize and treat tumors with great precision. Here, we present in vivo results showing that an emerging imaging modality, magnetic particle imaging (MPI), can be combined with magnetic hyperthermia into an image-guided theranostic platform. MPI is a noninvasive 3D tomographic imaging method with high sensitivity and contrast, zero ionizing radiation, and is linearly quantitative at any depth with no view limitations. The same superparamagnetic iron oxide nanoparticle (SPIONs) tracers imaged in MPI can also be excited to generate heat for magnetic hyperthermia. In this study, we demonstrate a theranostic platform, with quantitative MPI image guidance for treatment planning and use of the MPI gradients for spatial localization of magnetic hyperthermia to arbitrarily selected regions. This addresses a key challenge of conventional magnetic hyperthermia-SPIONs delivered systemically accumulate in off-target organs ( e.g., liver and spleen), and difficulty in localizing hyperthermia results in collateral heat damage to these organs. Using a MPI magnetic hyperthermia workflow, we demonstrate image-guided spatial localization of hyperthermia to the tumor while minimizing collateral damage to the nearby liver (1-2 cm distance). Localization of thermal damage and therapy was validated with luciferase activity and histological assessment. Apart from localizing thermal therapy, the technique presented here can also be extended to localize actuation of drug release and other biomechanical-based therapies. With high contrast and high sensitivity imaging combined with precise control and localization of the actuated therapy, MPI is a powerful platform for magnetic-based theranostics.

Keywords: image-guided; magnetic fluid hyperthermia; magnetic hyperthermia; magnetic nanoparticles; magnetic particle imaging; superparamagnetic iron oxide nanoparticles; targeted therapy; theranostics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Female
  • Heating*
  • Humans
  • Hyperthermia, Induced*
  • Magnetic Fields
  • Magnetite Nanoparticles / administration & dosage
  • Magnetite Nanoparticles / chemistry*
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Nude
  • Optical Imaging*

Substances

  • Antineoplastic Agents
  • Magnetite Nanoparticles