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Research Papers: Micro/Nanoscale Heat Transfer

Nanoparticle Redistribution in PC3 Tumors Induced by Local Heating in Magnetic Nanoparticle Hyperthermia: In Vivo Experimental Study

[+] Author and Article Information
Qimei Gu, 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,
Baltimore, MD 21250
e-mail: zliang@umbc.edu

1Corresponding author.

Contributed by the Heat Transfer Division of ASME for publication in the JOURNAL OF HEAT TRANSFER. Manuscript received June 4, 2018; final manuscript received December 11, 2018; published online January 14, 2019. Assoc. Editor: Bumsoo Han.

J. Heat Transfer 141(3), 032402 (Jan 14, 2019) (9 pages) Paper No: HT-18-1363; doi: 10.1115/1.4042298 History: Received June 04, 2018; Revised December 11, 2018

In magnetic nanoparticle hyperthermia, a required thermal dosage for tumor destruction greatly depends on nanoparticle distribution in tumors. The objective of this study is to conduct in vivo experiments to evaluate whether local heating using magnetic nanoparticle hyperthermia changes nanoparticle concentration distribution in prostatic cancer (PC3) tumors. In vivo animal experiments were performed on grafted PC3 tumors implanted in mice to investigate whether local heating via exposing the tumor to an alternating magnetic field (5 kA/m and 192 kHz) for 25 min resulted in nanoparticle spreading from the intratumoral injection site to tumor periphery. Nanoparticle redistribution due to local heating is evaluated via comparing microCT images of resected tumors after heating to those in the control group without heating. A previously determined calibration relationship between microCT Hounsfield unit (HU) values and local nanoparticle concentrations in the tumors was used to determine the distribution of volumetric heat generation rate (qMNH) when the nanoparticles were subject to the alternating magnetic field. sas,matlab, and excel were used to process the scanned data to determine the total heat generation rate and the nanoparticle distribution volumes in individual HU ranges. Compared to the tumors in the control group, nanoparticles in the tumors in the heating group occupied not only the vicinity of the injection site, but also tumor periphery. The nanoparticle distribution volume in the high qMNH range (>1.8 × 106 W/m3) is 10% smaller in the heating group, while in the low qMNH range of 0.6–1.8 × 106 W/m3, it is 95% larger in the heating group. Based on the calculated heat generation rate in individual HU ranges, the percentage in the HU range larger than 2000 decreases significantly from 46% in the control group to 32% in the heating group, while the percentages in the HU ranges of 500–1000 and 1000–1500 in the heating group are much higher than that in the control group. Heating PC3 tumors for 25 min resulted in significant nanoparticle migration from high concentration regions to low concentration regions in the tumors. The volumetric heat generation rate distribution based on nanoparticle distribution before or after local heating can be used in the future to guide simulation of nanoparticle redistribution and its induced temperature rise in PC3 tumors during magnetic nanoparticle hyperthermia, therefore, accurately predicting required thermal dosage for safe and effective thermal therapy.

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Figures

Grahic Jump Location
Fig. 1

Experiment setup consisting of a syringe pump for controlling infusion of ferrofluid, PC3 tumors implanted in mice, a radio frequency generator for inducing an alternating current, and generated alternating magnetic field

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Fig. 2

A high-resolution microCT system to scan both a resected PC3 tumor and a specimen of de-ionized water

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Fig. 3

The previously determined linear relationship between the q‴MNH and microCT HU value

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Fig. 4

Maximum intensity projection images of two tumors in the axial (left), sagittal (middle), and coronal (right) planes. The tumors were injected with 0.1 cc ferrofluid at an infusion rate of 3 mL/min, (top) a tumor in the control group without heating; and (bottom) a tumor in the heating group with 25 min of heating.

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Fig. 5

Linear relationship between the Hounsfield unit and grayscale value in microCT scans, based on known HU values of air and de-ionized water. The dash line is an extension of the linear line to a wide range.

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Fig. 6

Heat generation rate in individual HU ranges of tumors in both the control group without heating and the heating group. The symbol * (Student's t-test) or the symbol # (Wilcoxon rank sum test) denotes significant difference between the control and heating groups with a p-value less than 0.05.

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Fig. 7

Percentage change in energy generation rate in individual HU ranges from the control group tumors to the heating group tumors

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Fig. 8

Percentage of contribution of energy deposition rate in different Hounsfield unit ranges of the total energy deposition rate in individual tumors. The symbol * denotes significant difference with a p-value less than 0.05 based on Student's t-test and Wilcoxon rank sum test.

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