Development of a SQUID (Superconducting Quantum Interference Device) Detection System of Magnetic Nanoparticles for Cancer Imaging.

Abstract

In this dissertation, I present the development of a SQUID (Superconducting Quantum Interference Device) imaging system using targeted magnetic nanoparticles (NPs) as contrast agents. The contrast agents are functionalized for targeting by the conjugation of the magnetic NPs to folic acid (FA) molecules on dendrimer scaffolds. Cellular internalization is accomplished through the high-affinity folic acid receptors (FARs), which are overexpressed in various human carcinomas. SQUID can be applied to detect signals from the magnetic cores of the contrast agents and hence diagnose the tumor. Based on the magnetic properties of the magnetic NPs, two detection methods were developed: remanence and magnetorelaxometry (MRX). The remanence measurement-based method detects magnetic NPs that are sufficiently large and possess long relaxation time. Samples were vertically oscillated and horizontally translated each in one-dimension. The system was calibrated with y-Fe2O3 NPs (mean diameter 25 nm) and the detection limit was found to be 10 ng at a distance of 1.7 cm and the spatial resolution was ~1 cm. A theoretical model of this system was proposed and applied to image reconstruction of scanned phantoms with two NP injection spots. The developed SQUID system can determine not only the amount and horizontal position of the NPs, but also their depth in the phantoms. The MRX technique utilizes the NPs superparamagnetic property and records their time course magnetic decay. The system was investigated by using a number of iron oxide NP products with different mean diameters. The results showed that the MRX signal intensity is sensitively dependent on the size of the NPs. The best detection limit of 300 ng of total iron content was found on using a d = 12 nm Fe3O4 NP sample and this result was supported by computer simulations. To produce magnetic NPs for the MRX study, a synthetic approach of size-controllable Fe3O4 NPs was developed. Accordingly, the magnetic property can be tuned from ferromagnetic to superparamagnetic. In vitro experiments were conducted after functionalization of the synthesized NPs, which showed enhancement in cell targeting of the FA-modified NPs.