Localized hyperthermia with iron oxide-doped yttrium microparticles: steps toward image-guided thermoradiotherapy in liver cancer

J Vasc Interv Radiol. 2014 Mar;25(3):397-404. doi: 10.1016/j.jvir.2013.10.022. Epub 2013 Dec 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brachytherapy / methods
  • Cell Line, Tumor
  • Combined Modality Therapy / methods
  • Feasibility Studies
  • Ferric Compounds / therapeutic use*
  • Hyperthermia, Induced / methods*
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / 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*


  • Ferric Compounds
  • ferric oxide
  • Yttrium