Cargando…

Incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for DNA-targeted radiotherapy using Auger electron emitters.

A promising new treatment for glioma involves Auger electron emitters such as 125I or 123I conjugated to deoxyuridine (IUdR). However, the presence in tumour deposits of non-proliferating cells with clonogenic potential poses a major limitation to this cycle-specific therapy. We have used multicellu...

Descripción completa

Detalles Bibliográficos
Autores principales: Neshasteh-Riz, A., Angerson, W. J., Reeves, J. R., Smith, G., Rampling, R., Mairs, R. J.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group|1 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063300/
https://www.ncbi.nlm.nih.gov/pubmed/9052399
_version_ 1782137307554381824
author Neshasteh-Riz, A.
Angerson, W. J.
Reeves, J. R.
Smith, G.
Rampling, R.
Mairs, R. J.
author_facet Neshasteh-Riz, A.
Angerson, W. J.
Reeves, J. R.
Smith, G.
Rampling, R.
Mairs, R. J.
author_sort Neshasteh-Riz, A.
collection PubMed
description A promising new treatment for glioma involves Auger electron emitters such as 125I or 123I conjugated to deoxyuridine (IUdR). However, the presence in tumour deposits of non-proliferating cells with clonogenic potential poses a major limitation to this cycle-specific therapy. We have used multicellular tumour spheroids derived from the human glioma cell line UVW to study [125I]IUdR-targeted radiotherapy in aggregates containing cells in different proliferative states. Autoradiographic identification of labelled cells indicated that nuclear incorporation of [125I]IUdR decreased markedly with increasing size of spheroid. IUdR incorporation was maximal in the surface layer of cells and decreased with depth within spheroids. Radiopharmaceutical uptake corresponded closely to the regions of cell cycling as indicated by staining for the nuclear antigen Ki67. The uptake of drug was enhanced by increasing the duration of incubation from 52 h to 104 h. These observations suggest that significant sparing of non-cycling malignant cells would result from treatment delivered as a single injection of radiolabelled IUdR. To achieve maximal therapeutic effect. IUdR should be administered by multiple injections, by slow release from biodegradable implants or by slow-pump delivery. IMAGES:
format Text
id pubmed-2063300
institution National Center for Biotechnology Information
language English
publishDate 1997
publisher Nature Publishing Group|1
record_format MEDLINE/PubMed
spelling pubmed-20633002009-09-10 Incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for DNA-targeted radiotherapy using Auger electron emitters. Neshasteh-Riz, A. Angerson, W. J. Reeves, J. R. Smith, G. Rampling, R. Mairs, R. J. Br J Cancer Research Article A promising new treatment for glioma involves Auger electron emitters such as 125I or 123I conjugated to deoxyuridine (IUdR). However, the presence in tumour deposits of non-proliferating cells with clonogenic potential poses a major limitation to this cycle-specific therapy. We have used multicellular tumour spheroids derived from the human glioma cell line UVW to study [125I]IUdR-targeted radiotherapy in aggregates containing cells in different proliferative states. Autoradiographic identification of labelled cells indicated that nuclear incorporation of [125I]IUdR decreased markedly with increasing size of spheroid. IUdR incorporation was maximal in the surface layer of cells and decreased with depth within spheroids. Radiopharmaceutical uptake corresponded closely to the regions of cell cycling as indicated by staining for the nuclear antigen Ki67. The uptake of drug was enhanced by increasing the duration of incubation from 52 h to 104 h. These observations suggest that significant sparing of non-cycling malignant cells would result from treatment delivered as a single injection of radiolabelled IUdR. To achieve maximal therapeutic effect. IUdR should be administered by multiple injections, by slow release from biodegradable implants or by slow-pump delivery. IMAGES: Nature Publishing Group|1 1997 /pmc/articles/PMC2063300/ /pubmed/9052399 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Neshasteh-Riz, A.
Angerson, W. J.
Reeves, J. R.
Smith, G.
Rampling, R.
Mairs, R. J.
Incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for DNA-targeted radiotherapy using Auger electron emitters.
title Incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for DNA-targeted radiotherapy using Auger electron emitters.
title_full Incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for DNA-targeted radiotherapy using Auger electron emitters.
title_fullStr Incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for DNA-targeted radiotherapy using Auger electron emitters.
title_full_unstemmed Incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for DNA-targeted radiotherapy using Auger electron emitters.
title_short Incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for DNA-targeted radiotherapy using Auger electron emitters.
title_sort incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for dna-targeted radiotherapy using auger electron emitters.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063300/
https://www.ncbi.nlm.nih.gov/pubmed/9052399
work_keys_str_mv AT neshastehriza incorporationofiododeoxyuridineinmulticellulargliomaspheroidsimplicationsfordnatargetedradiotherapyusingaugerelectronemitters
AT angersonwj incorporationofiododeoxyuridineinmulticellulargliomaspheroidsimplicationsfordnatargetedradiotherapyusingaugerelectronemitters
AT reevesjr incorporationofiododeoxyuridineinmulticellulargliomaspheroidsimplicationsfordnatargetedradiotherapyusingaugerelectronemitters
AT smithg incorporationofiododeoxyuridineinmulticellulargliomaspheroidsimplicationsfordnatargetedradiotherapyusingaugerelectronemitters
AT ramplingr incorporationofiododeoxyuridineinmulticellulargliomaspheroidsimplicationsfordnatargetedradiotherapyusingaugerelectronemitters
AT mairsrj incorporationofiododeoxyuridineinmulticellulargliomaspheroidsimplicationsfordnatargetedradiotherapyusingaugerelectronemitters