Heating Protocol Design Affected by Nanoparticle Redistribution and Thermal Damage Model in Magnetic Nanoparticle Hyperthermia for Cancer Treatment

Abstract

Recent micro-CT scans have demonstrated a much larger magnetic nanoparticle distribution volume in tumors after localized heating than those without heating, suggesting possible heating-induced nanoparticle migration. In this study, a theoretical simulation was performed on tumors injected with magnetic nanoparticles to evaluate the extent to which the nanoparticle redistribution affects the temperature elevation and thermal dosage required to cause permanent thermal damage to PC3 tumors. 0.1 cc of a commercially available ferrofluid containing magnetic nanoparticles was injected directly to the center of PC3 tumors. The control group consisted of four PC3 tumors resected after the intratumoral injection, while the experimental group consisted of another four PC3 tumors injected with ferrofluid and resected after 25 min of local heating. The micro-CT scan generated tumor model was attached to a mouse body model. The blood perfusion rates in the mouse body and PC3 tumor were first extracted based on the experimental data of average mouse surface temperatures using an infrared camera. A previously determined relationship between nanoparticle concentration and nanoparticle-induced volumetric heat generation rate was implemented into the theoretical simulation. Simulation results showed that the average steady-state temperature elevation in the tumors of the control group is higher than that in the experimental group where the nanoparticles are more spreading from the tumor center to the tumor periphery (control group: 70.6±4.7 °C versus experimental group: 69.2±2.6 °C). Further, we assessed heating time needed to cause permanent thermal damage to the entire tumor, based on the nanoparticle distribution in each tumor. The more spreading of nanoparticles to tumor periphery in the experimental group resulted in a much longer heating time than that in the control group. The modified thermal damage model by Dr. John Pearce led to almost the same temperature elevation distribution; however, the required heating time was at least 24% shorter than that using the traditional Arrhenius integral, despite the initial time delay. The results from this study suggest that in future simulation, the heating time needed when considering dynamic nanoparticle migration during heating is probably between 19 and 29 min based on the Pearce model. In conclusion, the study demonstrates the importance of including dynamic nanoparticle spreading during heating and accurate thermal damage model into theoretical simulation of temperature elevations in tumors to determine thermal dosage needed in magnetic nanoparticle hyperthermia design.

A 3D Approach Using a Control Algorithm to Minimize the Effects on the Healthy Tissue in the Hyperthermia for Cancer Treatment

“…Additionally, at this temperature, there is a delay in achieving tissue damage, which was not considered in this paper. Moreover, there are more precise ways to quantify tumor ablation, such as the Arrhenius models [ 36 , 37 ], or considering a temperature-dependent time delay, such as the Pearce model [ 38 , 39 ]. Furthermore, the blood perfusion rate ( ) was considered constant, but recent studies have analyzed its dependencies on blood temperature [ 11 ] and thermal damage [ 36 ].…”

Nanoparticle Delivery in Prostate Tumors Implanted in Mice Facilitated by Either Local or Whole-Body Heating

“…Temperature elevations in the tumors in the local heating group were not uniform, with variations of more than 2 °C in the tumors of 10 mm in diameter using an illuminator. A much larger temperature elevation would be expected in deep-seated tumors during local heating [ 44 , 45 ]. In addition, local heating may also cause collateral thermal damage to surrounding healthy tissue when the tumor is located in a deep tissue region [ 46 ].…”

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