Abstract 2673: Positive contrast imaging of magnetic nanoplatforms for image-guided drug delivery.

Abstract

Abstract During the last 2 decades no new clinical MRI agents have been approved for clinical use. While Gadolinium based agents have been very popular, Gd cannot be used in emerging multi-functional nano platforms that have the potential to be retained in the body leading to severe toxicity. Superparamagnetic iron-oxide nanoparticles (SPIONs) are most attractive as offering a significant alternative that is far less toxic than Gd based agents. They can be incorporated into nanoplatforms combining other therapeutic agents to achieve image guided drug delivery. Conventionally, SPIONs are imaged via T2 and T2* weighted techniques which manifest signal voids for SPION-containing media. This proves to be disadvantageous in most circumstances because of the difficulty in discriminating signal loss from tissue associated partial voluming, perivascular effects, susceptibility artifacts and motion or flow artifacts. The unique combination of SPIONs with ultra-short TE (UTE) imaging has the specific advantages of rendering positive contrast with high SNR and high CNR, since non-SPION containing regions are dramatically dark due to native tissue's comparatively higher T1. With UTE, it may be possible to take advantage of SPION's inherent biocompatibility allowing for incorporation into drug loaded nanoplatforms leading to bright contrast and the possibility of in vivo quantification. Here, we report on a systematic study of positive contrast MR imaging using magnetic nanoplatforms incorporating SPIONs of varying particle size and functionalization. In the first step, nanoparticles of various sizes from 4 nm to 20 nm were synthesized by the thermal decomposition method in organic solvents and then coated with phospholipids containing PEG. The use of PEGylated phospholipid enables water solubility, imparts better dispersity and long circulation in blood stream. This results in a core-shell like morphology with iron oxide nanoparticle forming the core and phospholipid PEG forming the shell. The nanoparticles were characterized for their size and morphology using dynamic light scattering (DLS) and transmission electron microscopy (TEM). UTE was optimized on a Bruker 7T Biospec at the Center for Translational Neuroimaging (CTNI) at Northeastern University. High-contrast images were obtained by modification of various imaging parameters such as TE, TR, flip angle, pulse length, polar under-sampling, bandwidth and FOV/Geometry. The results are compared in vivo with Feraheme and show good promise for this approach to MR nanoparticle imaging. We acknowledge partial support from NSF DGE 0965843, HHS/5U54CA151881-02, and the Electronics Materials Research Institute at Northeastern University. Citation Format: Codi Gharagouzloo, Manasa Jillela, Rajiv Kumar, Dattatri Nagesha, Srinivas Sridhar. Positive contrast imaging of magnetic nanoplatforms for image-guided drug delivery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2673. doi:10.1158/1538-7445.AM2013-2673