Heike Richter

Magnetorelaxometry for localization and quantification of magnetic nanoparticles for thermal ablation studies

In magnetic heating treatments, intratumorally injected superparamagnetic iron oxide nanoparticles (MNP) exposed to an externally applied alternating magnetic field generate heat, specifically at the tumor region. This inactivates cancer cells with minimal side effects to the normal tissue. Therefore, the quantity of MNP needs to be thoroughly controlled to govern adequate heat production. Here, we demonstrate the capability of magnetorelaxometry (MRX) for the non-invasive quantification and localization of MNP accumulation in small animal models. The results of our MRX measurements using a multichannel vector magnetometer system with 304 SQUIDs (superconductive quantum interference device) on three mice hosting different carcinoma models (9L/lacZ and MD-AMB-435) are presented. The position and magnitude of the magnetic moment are reconstructed from measured spatial magnetic field distributions by a magnetic dipole model fit applying a Levenberg-Marquadt algorithm. Therewith, the center of gravity and the total amount of MNP accumulation in the mice are determined. Additionally, for a fourth mouse the distribution of MNP over individual organs and the tumor is analyzed by single-channel SQUID measurements, obtaining a sensitive spatial quantification. This study shows that magnetorelaxometry is well suited to monitor MNP accumulation before cancer therapy, with magnetic heating being an important precondition for treatment success.

Minimal-invasive magnetic heating of tumors does not alter intra-tumoral nanoparticle accumulation, allowing for repeated therapy sessions: an in vivo study in mice.

Localized magnetic heating treatments (hyperthermia, thermal ablation) using superparamagnetic iron oxide nanoparticles (MNPs) continue to be an active area of cancer research. For generating the appropriate heat to sufficiently target cell destruction, adequate MNP concentrations need to be accumulated into tumors. Furthermore, the knowledge of MNP bio-distribution after application and additionally after heating is significant, firstly because of the possibility of repeated heating treatments if MNPs remain at the target region and secondly to study potential adverse effects dealing with MNP dilution from the target region over time. In this context, little is known about the behavior of MNPs after intra-tumoral application and magnetic heating. Therefore, the present in vivo study on the bio-distribution of intra-tumorally injected MNPs in mice focused on MNP long term monitoring of pre and post therapy over seven days using multi-channel magnetorelaxometry (MRX). Subsequently, single-channel MRX was adopted to study the bio-distribution of MNPs in internal organs and tumors of sacrificed animals. We found no distinct change of total MNP amounts in vivo during long term monitoring. Most of the MNP amounts remained in the tumors; only a few MNPs were detected in liver and spleen and less than 1% of totally injected MNPs were excreted. Apparently, the application of magnetic heating and the induction of apoptosis did not affect MNP accumulation. Our results indicate that MNP mainly remained within the injection side after magnetic heating over a seven-days-observation and therefore not affecting healthy tissue. As a consequence, localized magnetic heating therapy of tumors might be applied periodically for a better therapeutic outcome.

Magnetorelaxometric quantification of magnetic nanoparticles in an artery model after ex vivo magnetic drug targeting

In magnetic drug targeting a chemotherapeutic agent is bound to coated magnetic nanoparticles, which are administered to the blood vessel system and subsequently focused by an external applied magnetic field. The optimization of intra-arterial magnetic drug targeting (MDT) requires detailed knowledge about the biodistribution of particles in the artery and the respective surrounding after the application. Here, we demonstrate the potential of magnetorelaxometry for quantifying the distribution of magnetic nanoparticles in the artery. To this end, we present a magnetorelaxometry investigation of a MDT study in an artery model. In particular, the absolute magnetic nanoparticle accumulation along the artery as well as the uptake profile along the region around the MDT-magnet position was quantified.

Quantification of magnetic nanoparticle concentration in pig lung tissue after magnetic aerosol drug targeting by magnetorelaxometry

Delivery of tiny aerosol droplets containing magnetic nanoparticles (MNP) to specific regions in the lungs guided by an external magnetic gradient field is a novel way of Magnetic Drug Targeting, which should allow to deposit high drug doses to a cancerous lung region together with reduced side-effects in unaffected tissue. Currently, this method is investigated in a pig lung model, a model being very similar to the human lung. The development of this procedure requires detailed knowledge about the biodistribution of MNP in different parts of the lung. Magnetorelaxometry (MRX) as a quantitative detection technique is used to determine the MNP distribution throughout the pig lungs after the aerosol targeting application. To this end, we extended our MRX measurement procedure to quantify the magnetic nanoparticle uptake in larger tissue samples with inhomogeneous particle distribution. Here, we present the results of the MRX quantification for an isolated pig lung. The absolute MNP uptake for individual lung lobes and the tissue concentration distribution over the whole lung is provided.

Distribution of Magnetic Nanoparticles after Magnetic Drug Targeting in an ExVivo Bovine Artery Model

The aim of Magnetic Drug Targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the over all dose is reduced. This can be achieved by coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intraarterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field should make them accumulate in the region of the steepest field gradient. Here, we suggest an artery model by which the magnetic targeting mechanism can be studied in detail. In particular, we focus on the quantification of the accumulation profile along the artery by SQUID-based magnetorelaxometry.

Multichannel Magnetorelaxometry In Vivo Monitoring of Magnetic Nanoparticle Quantity for Thermal Ablation Studies

To inactivate cancer cells with minimal side‐effects to the normal tissue, cancer therapy as magnetic thermal ablation utilizes superparamagnetic iron oxide nanoparticles (MNP) injected into the tumor. When exposed to an externally applied alternating magnetic field MNP generate heat, which deactivates cellular processes or even generates lethal thermal doses. Hence, the intratumoral quantity of MNP needs to be thoroughly controlled to govern adequate heat production in the carcinoma region. Here, we investigate the capability of multichannel magnetorelaxometry (MRX) for quantitative measurement of MNP accumulation in the tumor region performed in vivo on a carcinoma mouse, and moreover, the feasibility of quantitative long‐term monitoring of MNP amount in a conscious, freely moving mouse.

Calibration Phantom for Quantitative Tomography Analysis of Biodistribution of Magnetic Nanoparticles

Ferrofluids are being investigated for cancer treatments such as magnetic drug targeting (MDT) and magnetic heating treatments with the aim of treating the cancer locally, since magnetic nanoparticles with attached drugs are concentrated within the target region. Thus, the side effects are considerably reduced. One of the crucial factors for the success of these therapies is the magnetic nanoparticle distribution. Microcomputed X‐ray tomography (XμCT) has been introduced as adequate technique for non‐destructive three‐dimensional analysis of biological samples enriched with magnetic nanoparticles. The biological tissue specimens, in this case tumor bearing mice after intra‐tumoral magnetic nanoparticle injection, have been analyzed by means of XμCT. Complementary measurements have been performed by magnetorelaxometry (MRX). This technique enables a sensitive quantification of magnetic nanoparticles down to few nanograms. For multi‐phase samples, such as biological tissue enriched with magnetic nanoparticl...

Localization and Quantification of Magnetic Nanoparticles by Multichannel Magnetorelaxometry for in vivo Hyperthermia Studies in Carcinoma Models

In magnetic fluid hyperthermia / thermal ablation (MFH), superparamagnetic iron oxide nanoparticles (MNP) exposed to an externally applied alternating magnetic field generate heat specifically in the tumor region, which inactivates cancer cells with minimal side-effects to the normal tissue. The quantity of MNP needs to be thoroughly controlled to govern adequate heat production in the carcinoma region. We demonstrate the capability of magnetorelaxometry (MRX) for the non-invasive quantification and localization of MNP accumulation in small animal models. The results of our advanced MRX measurements using a 304-multichannel bio-magnetic SQUID system on two mice hosting two different carcinoma models (9L/lacZ, MD-AMB-435) are presented. The position and magnitude of the magnetic moment is reconstructed from the measured spatial magnetic field distribution by a magnetic dipole model fit applying a Levenberg-Marquadt algorithm. Therewith, the center of mass of the MNP accumulation in the tumor region of the mouse and moreover the amount of MNP in the determined region is quantified. This study shows that magnetorelaxometry is well suited for in vivo monitoring of MNP accumulation in hyperthermia application during cancer therapy.