title: Magnetic nanoparticle hyperthermia enhances radiation therapy: A study in mouse models of human prostate cancer.
abstract: OBJECTIVE
  We aimed to characterise magnetic nanoparticle hyperthermia (mNPH) with radiation therapy (RT) for prostate cancer.
  
  
  METHODS
  Human prostate cancer subcutaneous tumours, PC3 and LAPC-4, were grown in nude male mice. When tumours measured 150 mm3 magnetic iron oxide nanoparticles (MIONPs) were injected into tumours to a target dose of 5.5 mg Fe/cm3 tumour, and treated 24 h later by exposure to alternating magnetic field (AMF). Mice were randomly assigned to one of four cohorts to characterise (1) intratumour MIONP distribution, (2) effects of variable thermal dose mNPH (fixed AMF peak amplitude 24 kA/m at 160 ± 5 kHz) with/without RT (5 Gy), (3) effects of RT (RT5: 5 Gy; RT8: 8 Gy), and (4) fixed thermal dose mNPH (43 °C for 20 min) with/without RT (5 Gy). MIONP concentration and distribution were assessed following sacrifice and tissue harvest using inductively coupled plasma mass spectrometry (ICP-MS) and Prussian blue staining, respectively. Tumour growth was monitored and compared among treated groups.
  
  
  RESULTS
  LAPC-4 tumours retained higher MIONP concentration and more uniform distribution than did PC3 tumours. AMF power modulation provided similar thermal dose for mNPH and combination therapy groups (CEM43: LAPC-4: 33.6 ± 3.4 versus 25.9 ± 0.8, and PC3: 27.19 ± 0.7 versus 27.50 ± 0.6), thereby overcoming limitations of MIONP distribution and yielding statistically significant tumour growth delay.
  
  
  CONCLUSIONS
  PC3 and LAPC-4 tumours represent two biological models that demonstrate different patterns of nanoparticle retention and distribution, offering a model to make comparisons of these effects for mNPH. Modulating power for mNPH offers potential to overcome limitations of MIONP distribution to enhance mNPH.
authors: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , Maryland , and.
authors: Anilchandra
authors: A
authors: Attaluri
authors: Sri Kamal
authors: SK
authors: Kandala
authors: Michele
authors: M
authors: Wabler
authors: Haoming
authors: H
authors: Zhou
authors: Christine
authors: C
authors: Cornejo
authors: Michael
authors: M
authors: Armour
authors: Mohammad
authors: M
authors: Hedayati
authors: Yonggang
authors: Y
authors: Zhang
authors: Theodore L
authors: TL
authors: DeWeese
authors: Cila
authors: C
authors: Herman
authors: Robert
authors: R
authors: Ivkov
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D055909:Magnetic Field Therapy; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D011471:Prostatic Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D058185:Magnetite Nanoparticles; D011838:Radiation-Sensitizing Agents
keywords: Hyperthermia; magnetic nanoparticles; prostate cancer; radiation therapy; radiosensitiser