title: Localized hyperthermia with iron oxide-doped yttrium microparticles: steps toward image-guided thermoradiotherapy in liver cancer.
abstract: OBJECTIVE
  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.
  
  
  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: Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago; Department of Biomedical Engineering, Northwestern University, Evanston, Illinois. Electronic address: a-larson@northwestern.edu.
authors: Andrew C
authors: AC
authors: Gordon
authors: Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago.
authors: Robert J
authors: RJ
authors: Lewandowski
authors: Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago; Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago; Division of Organ Transplantation, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago.
authors: Riad
authors: R
authors: Salem
authors: Department of Materials Science and Engineering, Missouri University of Science and Technology, Rolla, Missouri.
authors: Delbert E
authors: DE
authors: Day
authors: Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee.
authors: Reed A
authors: RA
authors: Omary
authors: Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago; Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.
authors: Andrew C
authors: AC
authors: Larson
mesh_terms: D000818:Animals; D001918:Brachytherapy / Q000379:methods; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D005240:Feasibility Studies; D005290:Ferric Compounds / Q000627:therapeutic use*; D006979:Hyperthermia, Induced / Q000379:methods*; D008113:Liver Neoplasms / Q000473:pathology* / Q000628:therapy*; D053783:Magnetic Resonance Imaging, Interventional / Q000379:methods*; D008297:Male; D008863:Microspheres; D061089:Radiotherapy, Image-Guided / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D015019:Yttrium / Q000627:therapeutic use*
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide; D015019:Yttrium