title: Magnetic fluid hyperthermia (MFH)reduces prostate cancer growth in the orthotopic Dunning R3327 rat model.
abstract: BACKGROUND
  Magnetic fluid hyperthermia (MFH) is a new technique for interstitial hyperthermia or thermoablation based on AC magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. Preliminary studies in the Dunning tumor model of prostate cancer have demonstrated the feasibility of MFH in vivo. To confirm these results and evaluate the potential of MFH as a minimally invasive treatment of prostate cancer we carried out a systematic analysis of the effects of MFH in the orthotopic Dunning R3327 tumor model of the rat.
  
  
  METHODS
  Orthotopic tumors were induced by implantation of MatLyLu-cells into the prostates of 48 male Copenhagen rats. Animals were randomly allocated to 4 groups of 12 rats each, including controls. Treatment animals received two MFH treatments following a single intratumoral injection of a magnetic fluid. Treatments were carried out on days 10 and 12 after tumor induction using an AC magnetic field applicator system operating at a frequency of 100 kHz and a variable field strength (0--18 kA/m). On day 20, animals were sacrificed and tumor weights in the treatment and control groups were compared. In addition, tumor growth curves were generated and histological examinations and iron measurements in selected organs were carried out.
  
  
  RESULTS
  Maximum intratumoral temperatures of over 70 degrees C could be obtained with MFH at an AC magnetic field strength of 18 kA/m. At a constant field strength of 12.6 kA/m, mean maximal and minimal intratumoral temperatures recorded were 54.8 degrees C (centrally) and 41.2 degrees C (peripherally). MFH led to an inhibition of tumor growth of 44%-51% over controls. Mean iron content in the prostates of treated and untreated (injection of magnetic fluids but no AC magnetic field exposure) animals was 82.5%, whereas only 5.3% of the injected dose was found in the liver, 1.0% in the lung, and 0.5% in the spleen.
  
  
  CONCLUSIONS
  MFH led to a significant growth inhibition in this orthotopic model of the aggressive MatLyLu tumor variant. Intratumoral deposition of magnetic fluids was found to be stable, allowing for serial MFH treatments without repeated injection. The optimal treatment schedules and temperatures for MFH need to be defined in further studies.
authors.affiliation: Department of Urology, Charité University Medicine, Campus Mitte, Berlin, Germany. manfred.johannsen@charite.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Johannsen
authors.forename: Burghard
authors.initials: B
authors.lastname: Thiesen
authors.forename: Andreas
authors.initials: A
authors.lastname: Jordan
authors.forename: Kasra
authors.initials: K
authors.lastname: Taymoorian
authors.forename: Uwe
authors.initials: U
authors.lastname: Gneveckow
authors.forename: Norbert
authors.initials: N
authors.lastname: Waldöfner
authors.forename: Regina
authors.initials: R
authors.lastname: Scholz
authors.forename: Martin
authors.initials: M
authors.lastname: Koch
authors.forename: Michael
authors.initials: M
authors.lastname: Lein
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Loening
mesh_terms: D000818:Animals; D001831:Body Temperature; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006979:Hyperthermia, Induced / Q000379:methods*; D007501:Iron / Q000378:metabolism; D008280:Magnetics; D008297:Male; D009929:Organ Size; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007501:Iron