title: Radioactive holmium acetylacetonate microspheres for interstitial microbrachytherapy: an in vitro and in vivo stability study.
abstract: OBJECTIVE
  The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted.
  
  
  METHODS
  HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS.
  
  
  RESULTS
  After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days.
  
  
  CONCLUSIONS
  HoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment.
authors: Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands.
authors: Wouter
authors: W
authors: Bult
authors: Hendrik
authors: H
authors: de Leeuw
authors: Olav M
authors: OM
authors: Steinebach
authors: Martijn J
authors: MJ
authors: van der Bom
authors: Hubert Th
authors: HT
authors: Wolterbeek
authors: Ron M A
authors: RM
authors: Heeren
authors: Chris J G
authors: CJ
authors: Bakker
authors: Alfred D
authors: AD
authors: van Het Schip
authors: Wim E
authors: WE
authors: Hennink
authors: J Frank W
authors: JF
authors: Nijsen
mesh_terms: D000818:Animals; D001918:Brachytherapy / Q000379:methods*; D002277:Carcinoma / Q000473:pathology / Q000628:therapy*; D004355:Drug Stability; D005260:Female; D006695:Holmium / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006885:Hydroxybutyrates / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008863:Microspheres; D010422:Pentanones / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D006885:Hydroxybutyrates; D010422:Pentanones; D019275:Radiopharmaceuticals; C049529:acetyl acetonate; D006695:Holmium