Comparative evaluation of polymer coated versus antibody modified SPIONs for tumor detection using magnetic particle imaging

Abstract

Molecular imaging of cancer is a rapidly growing field given the enhanced specificity of disease detection it can achieve. As a radiation-free tomographic instrument, magnetic particle imaging (MPI) continues to demonstrate its effectiveness in molecular imaging. However, a long-standing issue within nanomedicine for tumor detection is the sparse uptake of superparamagnetic iron oxide nanoparticles (SPIONs) at the tumor site, thereby limiting its detection by MPI. To support achieving the full potential of MPI, SPION properties must be carefully modified for each application. The SPIONs size, magnetization, and surface coating impacts its biodistribution, tumor specificity and accumulation thereby influencing the generated MPI signal. Here we compare commercially available PrecisionMRX SPIONs in three coatings: a carboxylic acid functionalized SPION, a methoxypolyethylene glycol functionalized SPION and a Trastuzumab conjugated SPION. Our results demonstrated the influence SPION modifications have on magnetic relaxation and therefore the MPI sensitivity of the tracer. Modification of SPIONs also impacted their blood circulation time, inherently the carboxylic acid SPION cleared almost immediately from circulation, while the methoxypolyethylene glycol SPION displayed exceptional immune evasion and remained in the blood pool for over 6 hours. In a xenograft ovarian cancer mouse model, we achieved significant tumor uptake of the SPION through intravenous delivery and accurately quantified the iron amount both in and ex vivo using MPI and ICP-MS. This study furthers our understanding of SPION behavior in MPI and continues the exploration for a safe and potent tumor imaging strategy, presenting a powerful, biocompatible SPION platform that holds immense potential for the future of MPI.