■ Dr. Constantin Cope Medical Student Research Award Transcatheter intraarterial delivery of superparamagnetic iron oxide-labeled natural killer lymphocytes to hepatocellular carcinoma: longitudinal efficacy studies in a rat model

Abstract

Purpose Adoptive immunotherapy (AIT) with natural killer (NK) lymphocytes is a promising therapy for hepatocellular carcinoma (HCC). The purpose of this study was to test the hypotheses that superparamagnetic iron oxide (SPIO) nanoparticle labeling permits magnetic resonance imaging (MRI)-based quantification of NK delivery to HCC post infusion; intraarterial (IA) NK infusion demonstrates a therapeutic benefit compared to intravenous (IV) NK infusion; and NK delivery is correlated with tumor therapeutic response 8 days post infusion. Materials and Methods NK-92MIs were labeled with fluorescent SPIOs (GENOVIS, Sweden). 18 Sprague Dawley rats were implanted with McA-RH7777 tumors; 6 rats each comprised IA NK, IA saline, and IV NK groups. Catheter (Terumo Medical, NJ) was placed in hepatic artery or tail vein for IA NK/saline and IV NK infusions, respectively. MRI tumor size and T2* measurements were compared pre and 8 days post infusion. Tumor size changes, ΔT2*, and histological measurements were compared; Prussian blue staining was used for histological identification of labeled NK cells. CD56 and fluorescence microscopy qualitatively confirmed NK delivery. ANOVA, t-test, and Pearson correlation coefficients were used for statistical analyses. Results 91.7%, 85.7%, and 100.0% of tumors grew in IA NK, IA saline, and IV NK groups, respectively; initial tumor diameters were not different between groups (p=0.15), but final tumor diameters were different between all groups (p Conclusion The intrahepatic distribution of SPIO-labeled NKs was quantitatively visualized with MRI, and both labeled NK delivery as measured by histology and MRI were well-correlated with tumor response as determined by change in tumor diameter, with IA NKs demonstrating the strongest response. The developed techniques demonstrate potential for the adjustment of patient-specific therapeutic regimens during AIT for the treatment of HCC.