Abstract No. 116: MRI enables measurement of therapeutic nanoparticle uptake in rat N1S1 liver tumors during nano-ablation

Abstract

Nanoparticles functionalized with chemotherapeutic drugs and MRI contrast agents can serve dual therapeutic and diagnostic applications. Nano-ablation (NA) employs reversible electroporation to temporarily increase cell membrane permeability, offering interventional oncologists a method to enhance drug delivery to tumors. However, it remains unknown if MRI can be combined with NA to predict intratumoral uptake of superparamagnetic iron oxide nanoparticles (SPIOs) injected intravenously. We aimed to test the hypothesis that T2*-w MRI can be used to quantitatively predict intratumoral uptake of SPIOs. Using the N1S1 model of hepatoma, we induced 11 liver tumors in Sprague-Dawley rats. T2*-w MRI was performed using a Bruker 7T ClinScan to determine baseline tumor T2* signal intensity. Two minutes after SPIO injection into the femoral vein, NA was applied to the liver tumor at 1300 V/cm (8 pulses, 100 μs pulse duration) using bipolar electrodes. Animals were euthanized 10 minutes after NA and MRI determined post-procedural tumor T2* signal intensity. We measured the iron concentration of the harvested tissue from treated subjects as a proxy for SPIO uptake using inductively-coupled plasma mass spectroscopy (ICP-MS). Mean tumor iron concentration was correlated with the mean change in tumor T2* (measured in ms) using linear regression, with p<0.05 considered significant. Change in T2*-w MRI signal intensity significantly correlated with tumor SPIO uptake after NA (p=0.014, r=0.71). On average, for each unit of T2* signal intensity change (one millisecond) there was 7.33 μg of iron uptake per mg of tumor tissue. Intratumoral uptake of SPIOs after NA can be successfully quantified with 7T MRI and this uptake correlates with gold standard pathology. Thus, MRI may be used as a non-invasive method to measure the dose of therapeutic nanoparticles taken up by target liver tumors. Before clinical translation, future studies should attempt to replicate these findings using a larger animal model of liver cancer at clinically relevant 1.5T or 3T MRI field strengths.