Abstract
Recent microCT imaging study has demonstrated that local heating caused a much larger nanoparticle distribution volume in tumors than that in tumors without localized heating, suggesting possible nanoparticle redistribution/migration during heating. In this study, a theoretical simulation is performed to evaluate to what extent the nanoparticle redistribution affects the temperature elevations and thermal dosage required to cause permanent thermal damage to PC3 tumors. Two tumor groups with similar sizes are selected. The control group consists of five PC3 tumors with nanoparticles distribution without heating, while the experimental group consists of another five resected PC3 tumors with nanoparticles distribution obtained after 25 minutes of local heating. Each generated tumor model is attached to a mouse body model by microCT scans. A previously determined relationship between the nanoparticle concentration distribution and the volumetric heat generation rate is implemented in the theoretical simulation of temperature elevations during magnetic nanoparticle hyperthermia. Our simulation results show that the average steady state temperature elevation in the tumors of the control group is higher than that in the experimental group when the nanoparticles are more spreading from the tumor center to tumor periphery (control group: 64.03±3.2°C vs. experimental group: 62.04±3.07°C). Further we assess the thermal dosage needed to cause 100% permanent thermal damage (Arrhenius integral Ω = 4) to the entire tumor, based on the assumption of unchanged nanoparticle distribution during heating. The average heating time based on the experimental setting from our previous studies demonstrates significantly different designs. Specifically, the average heating time for the control group is 24.3 minutes. However, the more spreading of nanoparticles to tumor periphery in the experimental group results in a much longer heating time of 38.1 minutes, 57° longer than that in the control group, to induce permanent thermal damage to the entire tumor. The results from this study suggest that the heating time needed when considering dynamic nanoparticle migration during heating is probably between 24 to 38 minutes. In conclusion, the study demonstrates the importance of including dynamic nanoparticle spreading during heating into theoretical simulation of temperature elevations in tumors to determine accurate thermal dosage needed in magnetic nanoparticle hyperthermia design.
