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.

• Authors: Andrew C Gordon, Robert J Lewandowski, Riad Salem, Delbert E Day, Reed A Omary, Andrew C Larson
• Journal: Journal of vascular and interventional radiology : JVIR (J Vasc Interv Radiol) Vol. 25 Issue 3 Pg. 397-404 (Mar 2014) ISSN: 1535-7732 [Electronic] United States
• PMID: 24315666 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 SIR Published by SIR All rights reserved.

Chemical References

• Ferric Compounds
• ferric oxide
• Yttrium

Topics

• Animals
• Brachytherapy (methods)
• Cell Line, Tumor
• Combined Modality Therapy (methods)
• Feasibility Studies
• Ferric Compounds (therapeutic use)
• Hyperthermia, Induced (methods)
• Liver Neoplasms (pathology, therapy)
• Magnetic Resonance Imaging, Interventional (methods)
• Male
• Microspheres
• Radiotherapy, Image-Guided (methods)
• Rats
• Rats, Sprague-Dawley
• Reproducibility of Results
• Sensitivity and Specificity
• Treatment Outcome
• Yttrium (therapeutic use)