Publications [#65251] of Michael R. Zalutsky

Papers Published

1. Larsen, R.H. and Akabani, G. and Welsh, P. and Zalutsky, M.R., The cytotoxicity and microdosimetry of astatine-211-labeled chimeric monoclonal antibodies in human glioma and melanoma cells in vitro, Radiat. Res. (USA), vol. 149 no. 2 (1998), pp. 155 - 62
   (last updated on 2007/04/15)

   Abstract:
   The cytotoxicity of α-particle-emitting endoradiotherapeutic compounds is of increasing interest because clinical evaluation of these potential therapeutic agents is commencing. Astatine-211 is a radionuclide with a 7.2-h half-life that emits 5.87 and 7.45 MeV α-particles. In the present work, the authors have investigated the in vitro cytotoxicity of ²¹¹At-labeled chimeric monoclonal antibodies (mAbs) in monolayers of D-247 MG human glioma cells and SK-MEL-28 human melanoma cells. The mAbs studied were 81C6, reactive with the extracellular matrix antigen tenascin, Mel-14, directed against the cell membrane antigen proteoglycan chondroitin sulfate, and a nonspecific control mAb, TPS3.2. Cell uptake increased as a function of activity concentration after a 1-h exposure to the ²¹¹At-labeled mAbs. The retention of activity was also measured to calculate cumulative activity associated with the cells and the medium. The clonogenic survival as a function of activity concentration was linear in all cases with no detectable shoulder. Microdosimetric analyses were performed based on measured cell geometry, cumulative activity and Monte Carlo transport of a particles. Using 18 kBq/ml activity concentration and 1 h of incubation, a two to five times higher activity bound to the microcolonies was found for the specific mAbs compared to the nonspecific mAb. These calculations indicated that a survival fraction of 0.37 was achieved with 0.24-0.28 Gy for D-247 MG cells and 0.27-0.29 Gy for SK-MEL-28 cells. The microdosimetric cell sensitivity, to, for D-247 MG cells was significantly lower than for SK-MEL-28 cells (0.08 compared to 0.15 Gy). For both cell lines, reduction in survival to 0.37 required an average of only 1-2 α-particle hits to the cell nucleus

   Keywords:
   alpha-particle effects;astatine;biological effects of ionising particles;cellular effects of radiation;dosimetry;radioisotopes;