title: Photon activated therapy (PAT) using monochromatic synchrotron X-rays and iron oxide nanoparticles in a mouse tumor model: feasibility study of PAT for the treatment of superficial malignancy.
abstract: BACKGROUND
  X-rays are known to interact with metallic nanoparticles, producing photoelectric species as radiosensitizing effects, and have been exploited in vivo mainly with gold nanoparticles. The purpose of this study was to investigate the potential of sensitizing effect of iron oxide nanoparticles for photon activated therapy.
  
  
  METHODS
  X-rays photon activated therapy (PAT) was studied by treating CT26 tumor cells and CT26 tumor-bearing mice loaded with 13-nm diameter FeO NP, and irradiating them at 7.1 keV near the Fe K-edge using synchrotron x-rays radiation. Survival of cells was determined by MTT assay, and tumor regression assay was performed for in vivo model experiment. The results of PAT treated groups were compared with x-rays alone control groups.
  
  
  RESULTS
  A more significant reduction in viability and damage was observed in the FeO NP-treated irradiated cells, compared to the radiation alone group (p < 0.04). Injection of FeO NP (100 mg/kg) 30 min prior to irradiation elevated the tumor concentration of magnetite to 40 μg of Fe/g tissue, with a tumor-to-muscle ratio of 17.4. The group receiving FeO NP and radiation of 10 Gy showed 80% complete tumor regression (CTR) after 15-35 days and relapse-free survival for up to 6 months, compared to the control group, which showed growth retardation, resulting in 80% fatality. The group receiving radiation of 40 Gy showed 100% CTR in all cases irrespective of the presence of FeO NP, but CTR was achieved earlier in the PAT-treated group compared with the radiation alone group.
  
  
  CONCLUSIONS
  An iron oxide nanoparticle enhanced therapeutic effect with relatively low tissue concentration of iron and 10 Gy of monochromatic X-rays. Since 7.1 keV X-rays is attenuated very sharply in the tissue, FeO NP-PAT may have promise as a potent treatment option for superficial malignancies in the skin, like chest wall recurrence of breast cancer.
authors.affiliation: Department of Neurosurgery, School of Medicine, Catholic University of Daegu, Korea.
authors.forename: Gi-Hwan
authors.initials: GH
authors.lastname: Choi
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Seo
authors.forename: Ki-Hong
authors.initials: KH
authors.lastname: Kim
authors.forename: Hong-Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Lim
authors.forename: Jong-Ki
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control / Q000532:radiotherapy; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000532:radiotherapy; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry*; D005910:Glioma / Q000473:pathology / Q000517:prevention & control* / Q000532:radiotherapy; D006046:Gold / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D017785:Photons; D011838:Radiation-Sensitizing Agents; D017356:Synchrotrons; D014407:Tumor Cells, Cultured; D014964:X-Ray Therapy; D014965:X-Rays
chemical_list: D005290:Ferric Compounds; D011838:Radiation-Sensitizing Agents; C000499:ferric oxide; D006046:Gold