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.
Highlights
We have investigated the effect of concurrent administration of hyperthermia at 42°C on the cytotoxicity of 21'At-labelled chimeric 81C6 monoclonal antibody (MAb) in spheroids grown from the D-247 MG human glioma line
Hyperthermia treatments for time periods longer than I h resulted in a significant delay in spheroid growth
Spheroids heated for 4 h lost physical integrity, resulting in a large number of single cells and cell clumps spread on the agar
Summary
Cell line and spheroid propagationThe D-247 MG cell line, derived from a biopsy of a gliosarcoma, was established in the laboratory of Dr Darell Bigner and supplied by him for these studies (Bigner et al, 1988). RPMI-1640 medium (components purchased from JRH Biosciences, Lenexa, KS, USA) supplemented with 10% fetal calf serum, 2 mm L-glutamine, penicillin (50 U ml-') and streptomycin (50 jg ml-') was used for all experiments and hereafter is designated as complete medium. After determining their viability, 2 x 106 cells were added to 80 ml of complete medium in stirrer flasks at 30 r.p.m. and placed in an incubator at 37°C in a 5% carbon dioxide atmosphere. The spheroids used in the higher activity concentration experiment had an average radius of 103 ± 10 jm and an average volume of (4.69 ± 1.54) x 106 im at the start of the experiment
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