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.

References

1.
Espinosa
,
A.
,
Di Corato
,
R.
,
Kolosnjaj-Tabi
,
J.
,
Flaud
,
P.
,
Pellegrino
,
T.
, and
Wilhelm
,
C.
,
2016
, “
Duality of Iron Oxide Nanoparticles in Cancer Therapy: Amplification of Heating Efficiency by Magnetic Hyperthermia and Photothermal Bimodal Treatment
,”
ACS Nano
,
10
(
2
), pp.
2436
2446
.
2.
Hoopes
,
P. J.
,
Mazur
,
C. M.
,
Osterberg
,
B.
,
Song
,
A.
,
Gladstone
,
D. J.
,
Steinmetz
,
N. F.
,
Veliz
,
F. A.
,
Bursey
,
A. A.
,
R
,
J.
, and
Fiering
,
S. N.
,
2017
, “
Effect of Intra-Tumoral Magnetic Nanoparticle Hyperthermia and Viral Nanoparticle Immunogenicity on Primary and Metastatic Cancer
,”
Proc. SPIE Int. Soc. Opt. Eng.
(epub).
3.
LeBrun
,
A.
, and
Zhu
,
L.
,
2018
, “
Magnetic Nanoparticle Hyperthermia in Cancer Treatment: History, Mechanism, Imaging-Assisted Protocol Design, and Challenges
,”
Theory and Application of Heat Transfer in Cells and Organs
,
S.
Devashish
, ed.,
Wiley
,
Hoboken, NJ
, pp.
758
776
.
4.
Maier-Hauff
,
K.
,
Ulrich
,
F.
,
Nestler
,
D.
,
Niehoff
,
H.
,
Wust
,
P.
,
Thiesen
,
B.
,
Orawa
,
H.
,
Budach
,
V.
, and
Jordan
,
A.
,
2011
, “
Efficacy and Safety of Intratumoral Thermotherapy Using Magnetic Iron-Oxide Nanoparticles Combined With External Beam Radiotherapy on Patients With Recurrent Glioblastoma Multiforme
,”
J. Neuro-Oncol.
,
103
(
2
), pp.
317
324
.
5.
Petryk
,
A. A.
,
Misra
,
A.
,
Mazur
,
C. M.
,
Petryk
,
J. D.
, and
Hoopes
,
P. J.
,
2015
, “
Magnetic Nanoparticle Hyperthermia Cancer Treatment Efficacy Dependence on Cellular and Tissue Level Particle Concentration and Particle Heating Properties
,”
Proc. SPIE
,
9326
, p. 93260L.
6.
Dähring
,
H.
,
Grandke
,
J.
,
Teichgräber
,
U.
, and
Hilger
,
H.
,
2015
, “
Improved Hyperthermia Treatment of Tumors Under Consideration of Magnetic Nanoparticle Distribution Using Micro-CT Imaging
,”
Mol. Imaging Biol.
,
17
(
6
), pp.
763
769
.
7.
LeBrun
,
A.
,
Joglekar
,
T.
,
Bieberich
,
C.
,
Ma
,
R.
, and
Zhu
,
L.
,
2016
, “
Identification of Infusion Strategy for Achieving Repeatable Nanoparticle Distribution and Quantifiable Thermal Dosage in Magnetic Nanoparticle Hyperthermia
,”
Int. J. Hyperthermia
,
32
(
2
), pp.
132
143
.
8.
Pennes
,
H. H.
,
1948
, “
Analysis of Tissue and Arterial Blood Temperature in the Resting Human Forearm
,”
J. Appl. Physiol.
,
1
(
2
), pp.
93
122
.
9.
Song
,
C. W.
,
1984
, “
Effect of Local Hyperthermia on Blood Flow and Microenvironment: A Review
,”
Cancer Res.
,
44
(
Suppl. 10
), pp.
4721
4730
.http://cancerres.aacrjournals.org/content/44/10_Supplement/4721s.article-info
10.
Lang
,
J.
,
Erdmann
,
B.
, and
Seebass
,
M.
,
1999
, “
Impact of Nonlinear Heat Transfer on Temperature Control in Regional Hyperthermia
,”
IEEE Trans. Biomed. Eng.
,
46
(
9
), pp.
1129
1138
.
11.
Rodrigues
,
H. F.
,
Capistrano
,
G.
,
Mello
,
F. M.
,
Zufelato
,
N.
,
Silveira-Lacerda
,
E.
, and
Bakuzis
,
A. F.
,
2017
, “
Precise Determination of the Heat Delivery During In Vivo Magnetic Nanoparticle Hyperthermia With Infrared Thermography
,”
Phys. Med. Biol.
,
62
(
10
), pp.
4062
4082
.
12.
Rylander
,
M. N.
,
Feng
,
Y.
,
Zhang
,
Y.
,
Bass
,
J.
,
Stafford
,
R. J.
,
Volgin
,
A.
,
Hazle
,
J. D.
, and
Diller
,
K. R.
,
2006
, “
Optimizing Heat Shock Protein Expression Induced by Prostate Cancer Laser Therapy Through Predictive Computational Models
,”
J. Biomed. Opt.
,
11
(
4
), p.
041113
.
13.
LeBrun
,
A.
,
Ma
,
R.
, and
Zhu
,
L.
,
2016
, “
MicroCT Image Based Simulation to Design Heating Protocols in Magnetic Nanoparticle Hyperthermia for Cancer Treatment
,”
J. Therm. Biol.
,
62
, pp.
129
137
.
14.
LeBrun
,
A.
,
Joglekar
,
T.
,
Bieberich
,
C.
,
Ma
,
R.
, and
Zhu
,
L.
,
2017
, “
Treatment Efficacy for Validating MicroCT Based Theoretical Simulation Approach in Magnetic Nanoparticle Hyperthermia for Cancer Treatment
,”
ASME J. Heat Transfer
,
139
(
5
), p.
051101
.
15.
Jordan
,
A.
,
Scholz
,
R.
,
Wust
,
P.
,
Fähling
,
H.
,
Krause
,
J.
,
Wlodarczyk
,
W.
,
Sander
,
B.
,
Vogl
,
T.
, and
Felix
,
R.
,
1997
, “
Effects of Magnetic Fluid Hyperthermia (MFH) on C3H Mammary Carcinoma In Vivo
,”
Int. J. Hyperthermia
,
13
(
6
), pp.
587
605
.
16.
Winslow
,
T. B.
,
Eranki
,
A.
,
Ullas
,
S.
,
Singh
,
A. K.
,
Repasky
,
E. A.
, and
Sen
,
A.
,
2015
, “
A Pilot Study of the Effects of Mild Systemic Heating on Human Head and Neck Tumour Xenografts: Analysis of Tumour Perfusion, Interstitial Fluid Pressure, Hypoxia and Efficacy of Radiation Therapy
,”
Int. J. Hyperthermia
,
31
(
6
), pp.
693
701
.
17.
Ma
,
R.
,
Su
,
D.
, and
Zhu
,
L.
,
2012
, “
Multiscale Simulation of Nanoparticle Transport in Deformable Tissue During an Infusion Process in Hyperthermia Treatments of Cancer
,”
Nanoparticle Heat Transfer and Fluid Flow, Computational & Physical Processes in Mechanics &Thermal Science Series
, Vol.
4
,
W. J.
Minkowycz
,
E.
Sparrow
, and
J. P.
Abraham
, ed.,
CRC Press, Taylor & Francis Group
,
Boca Raton, FL
.
18.
Neeves
,
K. B.
,
Sawyer
,
A. J.
,
Foley
,
C. P.
,
Saltzman
,
W. M.
, and
Olbrichtet
,
W. L.
,
2007
, “
Dilation and Degradation of the Brain Extracellular Matrix Enhances Penetration of Infused Polymer Nanoparticles
,”
Brain Res.
,
1180
, pp.
121
132
.
19.
Su
,
D.
,
Ma
,
R.
,
Salloum
,
M.
, and
Zhu
,
L.
,
2010
, “
Multi-Scale Study of Nanoparticle Transport and Deposition in Tissues During an Injection Process
,”
Med. Biol. Eng. Comput.
,
48
, pp.
853
863
.
20.
Tien
,
C.
, and
Ramarao
,
B. V.
,
2007
,
Granular Filtration of Aerosols and Hydrosols
, 2nd ed.,
Elsevier
,
Oxford, UK
.
21.
Attaluri
,
A.
,
Ma
,
R.
,
Qiu
,
Y.
,
Li
,
W.
, and
Zhu
,
L.
,
2011
, “
Nanoparticle Distribution and Temperature Elevations in Prostate Tumors in Mice During Magnetic Nanoparticle Hyperthermia
,”
Int. J. Hyperthermia
,
27
(
5
), pp.
491
502
.
22.
Gu
,
Q.
,
Min Zaw
,
M.
,
Munuhe
,
T.
,
Ma
,
R.
, and
Zhu
,
L.
,
2017
, “
Nanoparticle Re-Distribution in Tissue-Equivalent Gels Induced by Magnetic Nanoparticle Hyperthermia
,”
Summer Biomechanics, Bioengineering, and Biotransport Conference
, Tucson, AZ, June 21–24, Paper No. 17-A-713-SB3C.
23.
Zhang
,
K.
, and
Waxman
,
D. J.
,
2010
, “
PC3 Prostate Tumor-Initiating Cells With Molecular Profile FAM65Bhigh/MF12low/LEF1low Increase Tumor Angiogenesis
,”
Mol. Cancer
,
9
(
1
), pp.
319
332
.
24.
Manuchehrabadi
,
N.
,
Attaluri
,
A.
,
Cai
,
H.
,
Edziah
,
R.
,
Lalanne
,
E.
,
Bieberich
,
C.
,
Ma
,
R.
,
Johnson
,
A. M.
, and
Zhu
,
L.
,
2013
, “
Tumor Shrinkage Studies and Histological Analyses After Laser Photothermal Therapy Using Gold Nanorods
,”
J. Biomed. Eng. Technol.
,
12
(
2
), pp.
157
176
.
25.
Mah
,
P.
,
Reeves
,
T. E.
, and
Mcdavid
,
W. D.
,
2010
, “
Deriving Hounsfield Units Using Grey Levels in Cone Beam Computed Tomography
,”
Dentomaxilofac. Radiol.
,
39
(
6
), pp.
323
335
.
26.
Urata
,
M.
,
Kijima
,
Y.
,
Hirata
,
M.
,
Shinden
,
Y.
,
Arima
,
H.
,
Nakajo
,
A.
,
Koriyama
,
C.
,
Arigami
,
T.
,
Uenosono
,
Y.
,
Okumura
,
H.
,
Maemura
,
K.
,
Ishigami
,
S.
,
Yoshinaka
,
H.
, and
Natsugoe
,
S.
,
2014
, “
Computed Tomography Hounsfield Units Can Predict Breast Cancer Metastasis to Axillary Lymph Nodes
,”
BMC Cancer
,
14
, p.
730
.
27.
El-Kareh
,
A. W.
,
Braunstein
,
S. L.
, and
Secomb
,
T. W.
,
1993
, “
Effect of Cell Arrangement and Interstitial Volume Fraction on the Diffusivity of Monoclonal Antibodies in Tissue
,”
Biophys. J.
,
64
(
5
), pp.
1638
1646
. [8324199]
28.
Zhang
,
A.
,
Mi
,
X.
,
Yang
,
G.
, and
Xu
,
L. X.
,
2009
, “
Numerical Study of Thermally Targeted Liposomal Drug Delivery in Tumor
,”
ASME J. Heat Transfer
,
131
(
4
), p.
043209
.
29.
Roh
,
H. D.
,
Boucher
,
Y.
,
Kaliniki
,
S.
,
Buchsbaum
,
R.
,
Bloomer
,
W. D.
, and
Jain
,
R. K.
,
1991
, “
Interstitial Hypertension in Cervical Carcinomas in Humans: Possible Correlation With Tumor Oxygenation and Radiation Response
,”
Cancer Res.
,
51
(24), pp.
6695
6698
.http://cancerres.aacrjournals.org/content/51/24/6695.long
30.
Johannsen
,
M.
,
Gneveckow
,
U.
,
Thiesen
,
B.
,
Taymoorian
,
K.
,
Cho
,
C. H.
,
Waldofner
,
N.
,
Scholz
,
R.
,
Jordan
,
A.
,
Lowning
,
S. A.
, and
Wust
,
P.
,
2007
, “
Thermotherapy of Prostate Cancer Using Magnetic Nanoparticles: Feasibility, Imaging, and Three-Dimensional Temperature Distribution
,”
Eur. Urol.
,
52
(
6
), pp.
1653
1662
.
31.
Attaluri
,
A.
,
Nusbaum
,
C.
,
Wabler
,
M.
, and
Ivkov
,
R.
,
2013
, “
Calibration of a Quasi-Adiabatic Magneto-Thermal Calorimeter Used to Characterize Magnetic Nanoparticle Heating
,”
ASME J. Nanotechnol. Eng. Med.
,
4
, p.
011006
.
32.
Bordelon
,
D. E.
,
Cornejo
,
C.
,
Gruttner
,
C.
,
Westphal
,
F.
,
DeWeese
,
T. L.
, and
Ivkov
,
R.
,
2011
, “
Magnetic Nanoparticle Heating Efficiency Reveals Magneto-Structural Differences When Characterized With Wide Ranging and High Amplitude Alternating Magnetic Fields
,”
J. Appl. Phys.
,
109
(
12
), p.
124904
.
33.
Landi
,
G. T.
,
2013
, “
Simple Models for the Heating Curve in Magnetic Hyperthermia Experiments
,”
J. Magn. Magn. Mater.
,
326
, pp.
14
21
.
34.
Etheridge
,
M. L.
,
Hurley
,
K. R.
,
Zhang
,
J.
,
Jeon
,
S.
,
Ring
,
H. L.
,
Hogan
,
C.
,
Haynes
,
C. L.
,
Garwood
,
M.
, and
Bischof
,
J. C.
,
2014
, “
Accounting for Biological Aggregation in Heating and Imaging of Magnetic Nanoparticles
,”
Technology
,
2
(
3
), pp.
214
228
.
35.
Jeon
,
S.
,
Hurley
,
K. R.
,
Bischof
,
J. C.
,
Haynes
,
C. L.
, and
Hogan
,
C. J.
,
2016
, “
Quantifying Intra- and Extracellular Aggregation of Iron Oxide Nanoparticles and Its Influence on Specific Absorption Rate
,”
Nanoscale
,
8
(
35
), pp.
16053
16064
.
36.
Deatsch
,
A.
, and
Evans
,
B. A.
,
2014
, “
Heating Efficiency in Magnetic Nanoparticle Hyperthermia
,”
J. Magn. Magn. Mater.
,
354
, pp.
163
172
.
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