title: Influence of neutron irradiation on holmium acetylacetonate loaded poly(L-lactic acid) microspheres.
abstract: Holmium-loaded microspheres are useful systems in radio-embolization therapy of liver metastases. For administration to a patient, the holmium-loaded microspheres have to be irradiated in a nuclear reactor to become radioactive. In this paper. the influence of neutron irradiation on poly(L-lactic acid) (PLLA) microspheres and films, with or without holmium acetylacetonate (HoAcAc), is investigated, in particular using differential scanning calorimetry (MDSC), scanning electron microscopy, gel permeation chromatography (GPC), infrared spectroscopy, and X-ray diffraction. After irradiation of the microspheres, only minor surface changes were seen using scanning electron microscopy, and the holmium complex remained immobilized in the polymer matrix as reflected by a relatively small release of this complex. GPC and MDSC measurements showed a decrease in molecular weight and crystallinity of the PLLA, respectively, which can be ascribed to radiation induced chain scission. Irradiation of the HoAcAc loaded PLLA matrices resulted in evaporation of the non-coordinated and one coordinated water molecule of the HoAcAc complex, as evidenced by MDSC and X-ray diffraction analysis. Infrared spectroscopy indicated that some degradation of the acetylacetonate anion occurred after irradiation. Although some radiation induced damage of both the PLLA matrix and the embedded HoAcAc-complex occurs, the microspheres retain their favourable properties (no marginal release of Ho, preservation of the microsphere size), which make these systems interesting candidates for the treatment of tumours by radio-embolization.
authors.affiliation: Department of Nuclear Medicine, University Medical Centre Utrecht, The Netherlands. f.nijsen@azu.nl
authors.forename: J F
authors.initials: JF
authors.lastname: Nijsen
authors.forename: A D
authors.initials: AD
authors.lastname: van Het Schip
authors.forename: M J
authors.initials: MJ
authors.lastname: van Steenbergen
authors.forename: S W
authors.initials: SW
authors.lastname: Zielhuis
authors.forename: L M J
authors.initials: LM
authors.lastname: Kroon-Batenburg
authors.forename: M
authors.initials: M
authors.lastname: van de Weert
authors.forename: P P
authors.initials: PP
authors.lastname: van Rijk
authors.forename: W E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D002152:Calorimetry, Differential Scanning; D004621:Embolization, Therapeutic / Q000295:instrumentation*; D005720:Gamma Rays; D006695:Holmium / Q000737:chemistry*; D006801:Humans; D006885:Hydroxybutyrates / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008113:Liver Neoplasms / Q000532:radiotherapy; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008970:Molecular Weight; D009502:Neutrons; D010422:Pentanones / Q000737:chemistry*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D011868:Radioisotopes / Q000627:therapeutic use*; D013053:Spectrophotometry; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D006885:Hydroxybutyrates; D010422:Pentanones; D011091:Polyesters; D011108:Polymers; D011868:Radioisotopes; C049529:acetyl acetonate; D019344:Lactic Acid; C033616:poly(lactide); D006695:Holmium