title: Cytotoxicity of alpha-particle-emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia.
abstract: The high linear energy transfer, alpha-particle-emitting radionuclide astatine-211 (211At) is of interest for certain therapeutic applications; however, because of the 55- to 70-microm path length of its alpha-particles, achieving homogeneous tracer distribution is critical. Hyperthermia may enhance the therapeutic efficacy of alpha-particle endoradiotherapy if it can improve tracer distribution. In this study, we have investigated whether hyperthermia increased the cytotoxicity of an 211At-labelled monoclonal antibody (MAb) in tumour spheroids with a radius (approximately 100 microm) greater than the range of 211At alpha-particles. Hyperthermia for 1 h at 42 degrees C was used because this treatment itself resulted in no regrowth delay. Radiolabelled chimeric MAb 81C6 reactive with the extracellular matrix antigen tenascin was added to spheroids grown from the D-247 MG human glioma cell line at activity concentrations ranging from 0.125 to 250 kBq ml(-1). A significant regrowth delay was observed at 125 and 250 kBq ml(-1) in both hyperthermia-treated and untreated spheroids. For groups receiving hyperthermia, no increase in cytotoxicity was seen compared with normothermic controls at any activity concentration. These results and those from autoradiographs indicate that hyperthermia at 42 degrees C for 1 h had no significant effect on the uptake or distribution of this antitenascin MAb in D-247 MG spheroids.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Hauck
authors.forename: R H
authors.initials: RH
authors.lastname: Larsen
authors.forename: P C
authors.initials: PC
authors.lastname: Welsh
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000512:Alpha Particles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D000918:Antibody Specificity; D001246:Astatine / Q000627:therapeutic use*; D001692:Biological Transport; D018316:Gliosarcoma / Q000473:pathology*; D006801:Humans; D006979:Hyperthermia, Induced; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D051379:Mice; D009940:Organoids / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D016499:Radioimmunotherapy; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D019063:Tenascin / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000528:radiation effects
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D019063:Tenascin; D001246:Astatine