title: Effective targeting of magnetic radioactive 90Y-microspheres to tumor cells by an externally applied magnetic field. Preliminary in vitro and in vivo results.
abstract: Magnetic biodegradable poly(lactic acid) microspheres that incorporate both magnetite and the beta-emitter 90Y were prepared. By applying a directional external magnetic field gradient in excess of 0.02 Tesla/cm across a 96-well plate containing neuroblastoma cells incubated with the 90Y magnetite loaded microspheres, the radiation dose to the cells could be enhanced or reduced relative to the dose from a uniform loading of the well with 90Y-DTPA. Using the MTT assay, cell survival was measured for the magnetic field directed from above (cell sparing) and from below (cell targeting) the well plate, resulting in 65 +/- 8% or 18 +/- 5% survival respectively. This method was then applied to an in vivo murine tumor model. The biodistribution of intraperitoneally injected magnetic radioactive microspheres, after 24 h in mice, showed that 73 +/- 32% of the radioactivity was found on the subcutaneous tumor that had a rare earth magnet fixed above it. In contrast, the tumor radioactivity with no attached magnet was 6 +/- 4%. Magnetically targeted radiopolymers such as 90Y-microspheres show great promise for regional or intracavitary radiotherapy.
authors.affiliation: Cleveland Clinic Foundation, Radiation Oncology Department, OH 44195, USA.
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: J L
authors.initials: JL
authors.lastname: Humm
authors.forename: R M
authors.initials: RM
authors.lastname: Macklis
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D046508:Culture Techniques / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007773:Lactates; D019344:Lactic Acid; D008223:Lymphoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D008280:Magnetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009447:Neuroblastoma; D004369:Pentetic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011091:Polyesters; D011108:Polymers; D011877:Radionuclide Imaging; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D007773:Lactates; D011091:Polyesters; D011108:Polymers; D015021:Yttrium Radioisotopes; D019344:Lactic Acid; C033616:poly(lactide); D004369:Pentetic Acid