Longitudinal Monitoring of Nanoparticle Accumulation in PC‐3 Tumors

Abstract

Currently there isn't any definitive and non‐destructive test for predicting the accumulation of nanoparticles within tumors, and longitudinal monitoring of delivery requires a baseline using current methodologies. Diagnostic tools that make quantitative, independent measurements are needed to move product to the market. We utilized a subcutaneous PC‐3 tumor modal in 5 mice to predict and quantify accumulation of ferumoxytol. Diffusion tensor imaging (DTI) was utilized pre‐contrast to map out the diffusion anisotropy on a per‐voxel basis throughout the tumor to generate a predictive map for passive accumulation. QUTE‐CE MRI, a novel imaging modality developed in our lab, along with T1 and T2 measurements was used to follow accumulation.We are developing a methodology for both predicting and unambiguously characterizing the heterogeneous accumulation of nanoparticles within tumors from the enhanced permeability and retention (EPR) effect. This impacts the market of cancer pharmaceuticals, currently limited by its predictive ability of exclusive drug delivery to the tumor.We accurately predicted the heterogeneous accumulation of ferumoxytol with DTI. QUTE‐CE MRI proved to be more efficacious than T1 or T2 measurements, producing a better or comparable CNR, as well as clear, unambiguous definition of uptake without the need for comparison to pre‐contrast images. We have developed a novel strategy for predicting and following the accumulation of nanoparticles within the tumor. Ferumoxytol may be used as surrogate, combined with our methodology, to predict the EPR effect of other nanoparticles for image guided drug delivery.