Publications [#65248] of Michael R. Zalutsky

Papers Published

1. Aurlien, E. and Larsen, R.H. and Akabani, G. and Olsen, D.R. and Zalutsky, M.R. and Bruland, O.S., Exposure of human osteosarcoma and bone marrow cells to tumour-targeted α-particles and γ-irradiation: analysis of cell survival and microdosimetry, Int. J. Radiat. Biol. (UK), vol. 76 no. 8 (2000), pp. 1129 - 41 [09553000050111604]
   (last updated on 2007/04/15)

   Abstract:
   The study was designed to compare the cytotoxic effects of an α-emitting radioimmunoconjugate, which binds to osteosarcoma hut not to bone marrow cells, with those of external γ-irradiation. The human osteosarcoma cell line, OHS-sl, and mononuclear cells from bone marrow (BM) harvested from healthy donors, were used for these experiments. Cells in suspension were added to various activity concentrations of the anti-osteosarcoma monoclonal antibody TP-3 radiolabelled with ²¹¹At. Following incubation for 1 h, unbound radioactivity was washed off and cell survival was determined from clonegenic assays. Microdosimetry was calculated based on binding and retention kinetics of ²¹¹At to the cells, as well as cellular and nuclear diameters. For comparison, cell suspensions were irradiated with a single dose of ⁶⁰Co γ-rays. ²¹¹At-labelled TP-3 showed heterogeneous binding to OHS-sl cells, with a considerable variation among experiments. About 78% of the initially bound ²¹¹At decayed while associated with the OHS-sl cells. D₀ values estimated by microdosimetry were 0.33 (0.22-0.48, range) Gy and 1.18 (0.89-1.89) Gy for OHS-sl and BM cells, respectively, whereas D₀ values after external beam irradiation were 0.86±0.07 Gy and 1.71±0.22 Gy. The relative biological effectiveness (RBE) of ²¹¹At-labelled TP-3 at 37% survival was 3.43 for OHS-sl and 1.55 for BM. High-LET targeted α-particle exposure killed osteosarcoma cells more effectively than bone marrow cells, although heterogeneous antigen expression among these tumour cells limited the magnitude of this effect

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