8:48 AM Abstract No. 191 - ■ Dr. Constantin Cope Medical Student Research Award High-field MRI accurately quantifies tumor uptake of therapeutic iron-oxide nanoparticles in the McA-RH7777 rat model of liver cancer

Abstract

Purpose The rationale for this study was to develop and validate methods to non-invasively quantify drug delivery to tumors. The ideal animal model of hepatocellular carcinoma (HCC) would have histological similarity to human HCC yet permit intraarterial (IA) delivery of therapies. The hypervascular McA-RH7777 tumor in the diminutive Buffalo rat resembles HCC histologically, while the N1S1 tumor in the larger Sprague-Dawley rat is hypovascular. We tested the hypotheses that: a) hypervascular McA tumors can be grown in Sprague-Dawley rats; and b) 7T magnetic resonance imaging (MRI) can quantify intra-tumoral uptake of doxorubicin-loaded superparamagnetic iron oxide nanoparticles (DOX-SPIOs) in this model. Materials and Methods We implanted McA cells into multiple sites in the livers of 18 Sprague-Dawley rats. In successfully inoculated animals, we delivered DOX-SPIOs to tumors via the intravenous (IV) (n=9) or IA (n=11) route. Three identical sets of nanoparticle phantoms were used to validate image analysis methods. We obtained pre- and post-treatment T2*-weighted images using 7T MRI, and obtained ΔR2* from mean signal intensities of tumors in these images. We measured tumor iron concentration ([Fe]), an indicator of DOX-SPIO uptake, using mass spectroscopy. The primary outcome variable was the Pearson coefficient (r) to assess linear correlation between ΔR2* and [Fe]. Results Tumors grew successfully in 13/18 animals (72%). Mean maximum tumor diameter (Dmax) was 0.83 ± 0.25 cm (range: 0.31-1.42 cm). Phantom studies revealed a strong positive correlation between ΔR2* and [Fe], with r=0.99 (p Conclusion McA tumors can successfully be grown in Sprague-Dawley rats. MRI quantification of intra-tumoral uptake strongly correlated with iron concentrations in pathological specimens, suggesting that MRI may be used to quantify uptake of iron-oxide nanotherapeutics. In the future, these imaging methods could potentially be used by interventional oncologists as a tool to quantify drug delivery in patients.