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

Abstract

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.

Means to increase the therapeutic efficiency of magnetic heating of tumors

“…Therefore, the observed aggregation behavior was related to the mechanism of agglutination of MNPs by serum compartments, for example IgG. Interestingly, no aggregation was induced for MNPs coated with dextran, polymeric ARA, or sodium phosphate, respectively [30].…”

Experimental investigations on a branched tube model in magnetic drug targeting

“…This fluid was diluted to obtain a volume concentration that reflects experimental investigations on an ex vivo bovine artery described in Ref. [5], where a non-commercial fluid with an iron content of 6.3 mg/ml magnetite nanoparticles was injected into a freshly isolated bovine artery obtained from a slaughterhouse. Fig.…”

“…[2,3], which describe an intra-arterial chemotherapy application to medicate cell carcinoma of rabbits, are promising. Furthermore, precise measurement methods have been developed that focus on tomographic [4] and magnetorelaxometric [5] quantification of the particle distribution within the body tissue. However, the understanding of hydrodynamics and transport phenomena [6][7][8][9][10] is still challenging with regard to two important mechanisms, where the first focus is to target the particles towards the chosen region and the second is to capture them in the target area.…”

“…For the presented measurements a ferrofluid concentration of 0.14 vol% is chosen to reflect experimental investigations on an ex vivo bovine artery described in Ref. [5], where a non-commercial fluid with an iron content of 6.3 mg/ml magnetite nanoparticles was injected. Fig.…”

Nanotechnology in Cancer Therapy: Overview and Applications

“…Anti-HER2 immunoliposomes containing magnetite nanoparticles, which act as tumor-targeting vehicles, have been used to combine anti-HER2 antibody therapy with hyperthermia (Ito et al, 2004). Magnetorelaxometry can also be used to monitor the accumulation of magnetic nanoparticles before cancer therapy, with magnetic heating being an important precondition for treatment success (Richter et al, 2010). Although nanoparticle-mediated thermal therapy is a promising treatment of cancers, challenges posed by this form of hyperthermia include the nontarget biodistribution of nanoparticles in the reticuloendothelial system when administered systemically, the inability to visualize or quantify the global concentration and spatial distribution of these particles within tumors, the lack of standardized thermal modeling as well as algorithms for determining dose, and the concerns regarding their biocompatibility (Krishnan et al, 2010;Jain, 2010).…”