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Research Papers: Bio-Heat and Mass Transfer

Treatment Efficacy for Validating MicroCT-Based Theoretical Simulation Approach in Magnetic Nanoparticle Hyperthermia for Cancer Treatment

[+] Author and Article Information
Alexander LeBrun, Ronghui Ma

Department of Mechanical Engineering,
University of Maryland Baltimore County,
Baltimore, MD 21250

Tejashree Joglekar, Charles Bieberich

Department of Biology,
University of Maryland Baltimore County,
Baltimore, MD 21250

Liang Zhu

Department of Mechanical Engineering,
University of Maryland Baltimore County,
1000 Hilltop Circle,
Baltimore, MD 21250
e-mail: zliang@umbc.edu

1Corresponding author.

Presented at the 2016 ASME 5th Micro/Nanoscale Heat & Mass Transfer International Conference. Paper No. MNHMT2016-6559.Contributed by the Heat Transfer Division of ASME for publication in the JOURNAL OF HEAT TRANSFER. Manuscript received April 6, 2016; final manuscript received October 24, 2016; published online February 7, 2017. Assoc. Editor: Chun Yang.

J. Heat Transfer 139(5), 051101 (Feb 07, 2017) (7 pages) Paper No: HT-16-1177; doi: 10.1115/1.4035246 History: Received April 06, 2016; Revised October 24, 2016

The objective is to validate a designed heating protocol in a previous study based on treatment efficacy of magnetic nanoparticle hyperthermia in prostate tumors. In vivo experiments have been performed to induce temperature elevations in implanted PC3 tumors injected with magnetic nanoparticles, following the same heating protocol designed in our previous microCT-based theoretical simulation. A tumor shrinkage study and histological analyses of tumor cell death are conducted after the heating. Tumor shrinkage is observed over a long period of 8 weeks. Histological analyses of the tumors after heating are used to evaluate whether irreversible thermal damage occurs in the entire tumor region. It has been shown that the designed 25 min heating (Arrhenius integral Ω ≥ 4 in the entire tumor) on tumor tissue is effective to cause irreversible thermal damage to PC3 tumors, while reducing the heating time to 12 min (Ω ≥ 1 in the entire tumor) results in an initial shrinkage, however, later tumor recurrence. The treated tumors with 25 min of heating disappear after only a few days. On the other hand, the tumors in the control group without heating show approximately an increase of more than 700% in volume over the 8-week observation period. In the undertreated group with 12 min of heating, its growth rate is smaller than that in the control group. In addition, results of the histological analysis suggest vast regions of apoptotic and necrotic cells, consistent with the regions of significant temperature elevations. In conclusion, this study demonstrates the importance of imaging-based design for individualized treatment planning. The success of the designed heating protocol for completely damaging PC3 tumors validates the theoretical models used in planning heating treatment in magnetic nanoparticle hyperthermia.

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Figures

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Fig. 1

Experimental setup of the study, including an RF generator, a two-turn coil to induce an alternating magnetic field, a stage for holding the mouse, a water circulating heating pad, a pump, and a water reservoir supplying 37 °C warm water

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Fig. 2

Average tumor volumes and their standard deviations in the control group of tumors without ferrofluid injection over the 8-week observation period; * represents a p-value less than 0.05 and ** represents a p-value less than 0.01

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Fig. 3

Tumor shrinkage/growth over 8 weeks after 12 min of heating in the undertreated group; * represents a p-value less than 0.05 and ** represents a p-value less than 0.01

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Fig. 4

Tumor shrinkage after 25 min of heating in the completely treated group; * represents a p-value less than 0.05 and ** represents a p-value less than 0.01

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Fig. 5

Tumor growth and shrinkage at (a) pretreatment, (b) 2 weeks, (c) 4 weeks, and (d) 8 weeks posttreatment. The right circle in each panel represents the control tumor while the left circle represents the treated tumor with 25 min of heating.

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Fig. 6

Tumor growth rates (mm3/day) in the three groups over the observation duration of 56 days

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Fig. 7

H&E staining images of tumors at 25× magnification for the control group without heating (top panel) and the sham group (bottom panel). The scale bars are 1 mm. The circle shows the necrotic regions.

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Fig. 8

Histologic images of immediately resected PC3 tumors after 25 min of heating (a) 25× and (b) 100× magnification. The scale bar in (a) is 1 mm and the scale bar in (b) is 200 μm. Arrows show red blood vessels.

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