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Intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts
Intratumour heterogeneity in the uptake of blood-borne technetium-labelled human serum albumin ((99m)Tc-HSA) was studied in human melanoma xenografts in an attempt to identify transport barriers leading to inadequate and heterogeneous uptake of macromolecular therapeutic agents in tumours. The Biosc...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2003
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377045/ https://www.ncbi.nlm.nih.gov/pubmed/12610516 http://dx.doi.org/10.1038/sj.bjc.6600680 |
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author | Graff, B A Kvinnsland, Y Skretting, A Rofstad, E K |
author_facet | Graff, B A Kvinnsland, Y Skretting, A Rofstad, E K |
author_sort | Graff, B A |
collection | PubMed |
description | Intratumour heterogeneity in the uptake of blood-borne technetium-labelled human serum albumin ((99m)Tc-HSA) was studied in human melanoma xenografts in an attempt to identify transport barriers leading to inadequate and heterogeneous uptake of macromolecular therapeutic agents in tumours. The Bioscope imaging system, which can detect the distribution of (99m)Tc in 10-μm-thick tissue sections with a spatial resolution of just above 50 μm, was used to image the (99m)Tc-HSA uptake. Xenografted tumours of four human melanoma cell lines were included in the study. Significant intratumour heterogeneity in the uptake of (99m)Tc-HSA was detected. The heterogeneity had two distinctly different components, one random and one radial component. The uptake was lowest in the centre of the tumours and increased towards the tumour periphery. This radial heterogeneity was superimposed by a random heterogeneity, that is, spots with high uptake colocalised with spots with high vascular density and regions without significant uptake colocalised with necrotic regions. The magnitude of the heterogeneity did not change significantly with time after the administration of (99m)Tc-HSA. The tumours showed a random and a radial heterogeneity in blood perfusion similar to that in the uptake of (99m)Tc-HSA. The observations reported here suggest that the intratumour heterogeneity in the distribution of (99m)Tc-HSA was initiated primarily because of heterogeneity in the supply of (99m)Tc-HSA through the microvasculature, and that the presence of severe transport barriers in the tumour interstitium prevented significant equalisation of the initial heterogeneity with time. Consequently, strategies for improving the delivery of macromolecular therapeutic agents to tumours should focus on increasing the tumour blood perfusion to increase the total uptake and improving the diffusion conditions in the tumour interstitium to diminish the heterogeneity in the uptake. |
format | Text |
id | pubmed-2377045 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23770452009-09-10 Intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts Graff, B A Kvinnsland, Y Skretting, A Rofstad, E K Br J Cancer Experimental Therapeutics Intratumour heterogeneity in the uptake of blood-borne technetium-labelled human serum albumin ((99m)Tc-HSA) was studied in human melanoma xenografts in an attempt to identify transport barriers leading to inadequate and heterogeneous uptake of macromolecular therapeutic agents in tumours. The Bioscope imaging system, which can detect the distribution of (99m)Tc in 10-μm-thick tissue sections with a spatial resolution of just above 50 μm, was used to image the (99m)Tc-HSA uptake. Xenografted tumours of four human melanoma cell lines were included in the study. Significant intratumour heterogeneity in the uptake of (99m)Tc-HSA was detected. The heterogeneity had two distinctly different components, one random and one radial component. The uptake was lowest in the centre of the tumours and increased towards the tumour periphery. This radial heterogeneity was superimposed by a random heterogeneity, that is, spots with high uptake colocalised with spots with high vascular density and regions without significant uptake colocalised with necrotic regions. The magnitude of the heterogeneity did not change significantly with time after the administration of (99m)Tc-HSA. The tumours showed a random and a radial heterogeneity in blood perfusion similar to that in the uptake of (99m)Tc-HSA. The observations reported here suggest that the intratumour heterogeneity in the distribution of (99m)Tc-HSA was initiated primarily because of heterogeneity in the supply of (99m)Tc-HSA through the microvasculature, and that the presence of severe transport barriers in the tumour interstitium prevented significant equalisation of the initial heterogeneity with time. Consequently, strategies for improving the delivery of macromolecular therapeutic agents to tumours should focus on increasing the tumour blood perfusion to increase the total uptake and improving the diffusion conditions in the tumour interstitium to diminish the heterogeneity in the uptake. Nature Publishing Group 2003-01-27 2003-01-28 /pmc/articles/PMC2377045/ /pubmed/12610516 http://dx.doi.org/10.1038/sj.bjc.6600680 Text en Copyright © 2003 Cancer Research UK 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 | Experimental Therapeutics Graff, B A Kvinnsland, Y Skretting, A Rofstad, E K Intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts |
title | Intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts |
title_full | Intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts |
title_fullStr | Intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts |
title_full_unstemmed | Intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts |
title_short | Intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts |
title_sort | intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377045/ https://www.ncbi.nlm.nih.gov/pubmed/12610516 http://dx.doi.org/10.1038/sj.bjc.6600680 |
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