Cytotoxicity of alpha-particle-emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia.

dc.contributor.author

Hauck, ML

dc.contributor.author

Larsen, RH

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Welsh, PC

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Zalutsky, MR

dc.coverage.spatial

England

dc.date.accessioned

2015-12-03T18:27:54Z

dc.date.issued

1998-03

dc.description.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.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/9514054

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0007-0920

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https://hdl.handle.net/10161/11043

dc.language

eng

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Springer Science and Business Media LLC

dc.relation.ispartof

Br J Cancer

dc.subject

Alpha Particles

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Animals

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Antibodies, Monoclonal

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Antibody Specificity

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Astatine

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Biological Transport

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Gliosarcoma

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Humans

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Hyperthermia, Induced

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Immunoglobulin G

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Mice

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Organoids

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Radioimmunotherapy

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Recombinant Fusion Proteins

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Tenascin

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Tumor Cells, Cultured

dc.title

Cytotoxicity of alpha-particle-emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia.

dc.type

Journal article

duke.contributor.orcid

Zalutsky, MR|0000-0002-5456-0324

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/9514054

pubs.begin-page

753

pubs.end-page

759

pubs.issue

5

pubs.organisational-group

Clinical Science Departments

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Duke

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Duke Cancer Institute

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Institutes and Centers

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Pathology

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Radiation Oncology

pubs.organisational-group

Radiology

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School of Medicine

pubs.publication-status

Published

pubs.volume

77

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