In vivo imaging and quantification of iron oxide nanoparticle uptake and biodistribution

Abstract

Recent advances in nanotechnology have allowed for the effective use of iron oxide nanoparticles (IONPs) for cancer imaging and therapy. When activated by an alternating magnetic field (AMF), intra-tumoral IONPs have been effective at controlling tumor growth in rodent models. To accurately plan and assess IONP-based therapies in clinical patients, noninvasive and quantitative imaging technique for the assessment of IONP uptake and biodistribution will be necessary. Proven techniques such as confocal, light and electron microscopy, histochemical iron staining, ICP-MS, fluorescent labeled mNPs and magnetic spectroscopy of Brownian motion (MSB), are being used to assess and quantify IONPs in vitro and in ex vivo tissues. However, a proven noninvasive in vivo IONP imaging technique has not yet been developed. In this study we have demonstrated the shortcomings of computed tomography (CT) and magnetic resonance imaging (MRI) for effectively observing and quantifying iron/IONP concentrations in the clinical setting. Despite the poor outcomes of CT and standard MR sequences in the therapeutic concentration range, ultra-short T2 MRI methods such as, Sweep Imaging With Fourier Transformation (SWIFT), provide a positive iron contrast enhancement and a reduced signal to noise ratio. Ongoing software development and phantom and in vivo studies, will further optimize this technique, providing accurate, clinically-relevant IONP biodistribution information.

Comparison of magnetic nanoparticle and microwave hyperthermia cancer treatment methodology and treatment effect in a rodent breast cancer model

“…40 Furthermore, the development and use of mNP imaging prior to activation will not only allow for real time determination of mNP distribution, but will also allow for improved treatment planning. 41, 42 If accurate and reproducible mNP treatment planning, based on mNP SAR, mNP concentration, location and field strength can be realized, the dependence on invasive thermal measurements may be reduced or even eliminated. This situation would enable more cost and time efficient treatments without sacrificing safety or efficacy.…”

Evaluating Broader Impacts of Nanoscale Thermal Transport Research

“…For this reason, magnetic nanoparticles have also been pursued, because they have the ability to interact with physiologically innocuous deep penetrating electromagnetic fields (several centimeters) to provide heating in a number of new applications. Further, these iron oxide nanoparticles can be targeted to cancer or even bacterial cells to induce destruction [261][262][263]. Questions as to the extent to which these nanoparticles produce heating localized on the nanoscale versus bulk and whether this Downloaded by [New York University] at 07: 56 12 June 2015 produces enhanced therapeutic effects persist in the field [263,264].…”

“…Further, these iron oxide nanoparticles can be targeted to cancer or even bacterial cells to induce destruction [261][262][263]. Questions as to the extent to which these nanoparticles produce heating localized on the nanoscale versus bulk and whether this Downloaded by [New York University] at 07: 56 12 June 2015 produces enhanced therapeutic effects persist in the field [263,264]. Answering these questions will provide new information that guides improved design and use of nanoparticles in a growing number of heating-based biomedical applications.…”

The Dartmouth Center for Cancer Nanotechnology Excellence: Magnetic Hyperthermia

“…The Hoopes group collaborates with the University of Minnesota, Center for Magnetic Resonance Research (Professor Michael Garwood) to assist in the development and in vivo utilization of a novel mNP-imaging technique: SWIFT-MRI [33]. SWIFT-imaging is being coupled with sophisticated radiation treatment planning software and techniques (Eclipse) and AMF-based hyperthermia modeling to achieve an innovative mNP hyperthermia-based planning system.…”