Localized Hyperthermia with Iron Oxide-Doped Yttrium Microparticles: Steps toward Image-Guided Thermoradiotherapy in Liver Cancer

Abstract

Purpose

To test whether iron oxide (IO)-containing yttrium aluminosilicate (YAS) microparticles (MPs) can generate localized therapeutic hyperthermia (≥ 43 C) when injected intratumorally in an animal model of liver cancer and whether MP distributions could be visualized with magnetic resonance (MR) imaging.

Materials and Methods

Twenty-one Sprague-Dawley rats implanted with N1-S1 liver tumors were assigned to alternating magnetic field (AMF) exposure following intratumoral injection with IO-YAS MPs (n = 7), sham surgery (n = 7), or baseline iron quantification (n = 7). Three fiberoptic probes allowed spatial and temporal monitoring of temperatures during 24 minutes of AMF exposure. T2-weighted turbo spin-echo MR imaging was performed within 1 hour after the procedure to detect signal voids caused by IO-YAS deposition. Hematoxylin and eosin-stained pathologic slides were also obtained, and the presence of IO-YAS was evaluated with inductively coupled plasma optical emission spectroscopy.

Results

Following AMF exposure, intratumoral temperatures after IO-YAS MP injection achieved therapeutic hyperthermia whereas those after sham surgery did not (46.6 C ± 1.3 vs 36.8 C ± 0.4; P < .0001). Within the treated group, the normal hepatic parenchyma (NHP) and rectal temperatures were 37.4 C ± 0.9 and 36.5 C ± 1.0 (P =.0809) at the conclusion of AMF exposure, respectively. A T2-weighted signal void at the tumor site was observed in all seven treated animals, and intratumoral IO-YAS was visualized on subsequent histopathologic examination in each case. The mean ratio of tumor:NHP Fe concentrations attributable to IO-YAS MPs was 108:1.

Conclusions

AMF exposure of intratumoral IO-YAS MPs generates localized therapeutic hyperthermia in an animal model of liver cancer. MR detectability and potential for combination brachytherapy warrants further investigation for thermoradiotherapy in liver cancer.

Department(s)

Materials Science and Engineering

Keywords and Phrases

iron oxidemethacrylic acid; unclassified drug; yttrium; yttrium aluminosilicate; animal experiment; animal model; atomic emission spectrometry; controlled study; hepatoma cell; histopathology; hyperthermic therapy; image guide thermoradiotherapy; image guided radiotherapy; liver cancer; liver tumor; magnetic field; male; nonhuman; nuclear magnetic resonance imaging

International Standard Serial Number (ISSN)

1051-0443

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2014 Elsevier, All rights reserved.

Publication Date

01 Jan 2014

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