BIOM-46. MRI RELAXATION PARAMETERS COULD REVEAL INFORMATION ON INTACT IRON OXIDE PARTICLES LABELED MESENCHYMAL STEM CELLS

Abstract INTRODUCTION Mesenchymal stem cells (MSCs) are promising for cancer immunotherapy as they can target tumors and deliver therapeutic agents like oncolytic viruses. Monitoring viable MSCs is crucial since they release their payload upon disintegration at the tumor site. Iron oxide particle (IOP)-labeled MSCs can be tracked using magnetic resonance imaging (MRI). Depending on the viability of the MSCs, the IOPs may be contained within the MSCs and/or exist freely suspended in brain tumors. This study aims to explore the MRI relaxation parameters as a biomarker for detecting viable iron-labeled MSCs after homing into the tumor. METHODS MSCs were loaded with MegaPro IOPs using a dual-labeling protocol. Five phantoms were created with concentrations ranging from 0.1 to 0.5 mM of IOP inside MSCs and/or as freely suspended particles. Three scenarios were simulated: 1) 100% iron-loaded MSCs representing all intact cells after homing; 2) 67% or 33% iron-loaded MSCs and the rest of the iron freely suspended, representing partial disintegration of MSCs after homing; and 3) freely suspended iron particles representing complete disintegration of MSCs after homing. Multi-gradient and spin-echo MRI was used to map R2 and R2*. Relaxation parameter (RR=R2*/R2) and iron concentrations (CR=CR2*/CR2) ratios computed from relaxation time parameters. RESULTS For intact cell conditions, RR (≥3) and CR (≥2) were higher than for the phantoms with freely suspended iron, with RR (≤2) and CR (≤1) for all concentrations. Within intact cell conditions, both ratios increased with the percentage of iron-labeled MSCs for less than 0.3 mM of IOP, and no difference was observed for concentrations above 0.3 mM of IOPs. CONCLUSION This study presents a clinically translatable biomarker for the viability status of IOP-loaded MSCs. MRI relaxation parameters are sensitive to the IOP-loaded MSCs’ viability status, even at a very low concentration of 0.1 mM of IOP.