title: Magnetically directed poly(lactic acid) 90Y-microspheres: novel agents for targeted intracavitary radiotherapy.
abstract: High energy beta-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. We developed as carriers for the ionic form of 90Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe3O4 (magnetite) which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10-40 microns MMS were radiochemically loaded to high specific activity with 90Y at a pH of 5.7. Stability studies showed that approximately 95% of added 90Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 degrees C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. We are currently optimizing this system for use in the treatment of neoplastic meningitis.
authors.affiliation: Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts.
authors.forename: U O
authors.initials: UO
authors.lastname: Häfeli
authors.forename: S M
authors.initials: SM
authors.lastname: Sweeney
authors.forename: B A
authors.initials: BA
authors.lastname: Beresford
authors.forename: E H
authors.initials: EH
authors.lastname: Sim
authors.forename: R M
authors.initials: RM
authors.lastname: Macklis
mesh_terms: D000818:Animals; D001918:Brachytherapy; D004574:Electromagnetic Fields; D052203:Ferrosoferric Oxide; D007501:Iron; D007773:Lactates / Q000737:chemistry*; D019344:Lactic Acid; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009447:Neuroblastoma / Q000532:radiotherapy; D010087:Oxides; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties; D014407:Tumor Cells, Cultured; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007773:Lactates; D010087:Oxides; D011091:Polyesters; D011108:Polymers; D015021:Yttrium Radioisotopes; D019344:Lactic Acid; C033616:poly(lactide); D007501:Iron; D052203:Ferrosoferric Oxide