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Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues
The objective of this study was to investigate the molecular weight (MW) and time‐dependence of the phenomenon termed “the enhanced permeability and retention”(EPR) effect in solid tumor, in particular to determine and define the early phase accumulation of macromolecules in tumor and normal tissues...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
1998
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921799/ https://www.ncbi.nlm.nih.gov/pubmed/9600125 http://dx.doi.org/10.1111/j.1349-7006.1998.tb00563.x |
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author | Noguchi, Youichiro Wu, Jun Duncan, Ruth Strohalm, Jiří Ulbrich, Karel Akaike, Takaaki Maeda, Hiroshi |
author_facet | Noguchi, Youichiro Wu, Jun Duncan, Ruth Strohalm, Jiří Ulbrich, Karel Akaike, Takaaki Maeda, Hiroshi |
author_sort | Noguchi, Youichiro |
collection | PubMed |
description | The objective of this study was to investigate the molecular weight (MW) and time‐dependence of the phenomenon termed “the enhanced permeability and retention”(EPR) effect in solid tumor, in particular to determine and define the early phase accumulation of macromolecules in tumor and normal tissues and the relationship between blood concentration and tissue clearance. As a model, radioiodinated N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymers of MW ranging from 4.5 K to 800 K were administered i.v. to mice bearing sarcoma 180 tumor. Within 10 min all HPMA copolymers accumulated effectively in the tumor regardless of MW (1.0–1.5% of injected dose per g of tumor). However, higher MW copolymers (>50 K) showed significantly increased tumor accumulation after 6 h, while the lower MW copolymers (<40 K) were cleared rapidly from tumor tissue due to rapid diffusion back into the bloodstream. Blood clearance was also MW‐dependent; the lower MW copolymers displayed rapid clearance, with kidney radioactivity of the copolymers of MW <20 K representing 24% of injected dose per g kidney at 1 min after i.v. administration. Within 10 min these copolymers passed through the kidney and were excreted in the urine. Higher MW copolymers consistently showed kidney levels of 3–5% dose per g kidney in the early phase with no time‐dependent accumulation in kidney. There was also no progressive accumulation in muscle or liver, regardless of polymer MW. These results suggest the “EPR effect” in solid tumor primarily arises from in the difference in clearance rate between the solid tumor and the normal tissues after initial penetration of the polymers into these tissues. |
format | Online Article Text |
id | pubmed-5921799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1998 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59217992018-05-11 Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues Noguchi, Youichiro Wu, Jun Duncan, Ruth Strohalm, Jiří Ulbrich, Karel Akaike, Takaaki Maeda, Hiroshi Jpn J Cancer Res Article The objective of this study was to investigate the molecular weight (MW) and time‐dependence of the phenomenon termed “the enhanced permeability and retention”(EPR) effect in solid tumor, in particular to determine and define the early phase accumulation of macromolecules in tumor and normal tissues and the relationship between blood concentration and tissue clearance. As a model, radioiodinated N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymers of MW ranging from 4.5 K to 800 K were administered i.v. to mice bearing sarcoma 180 tumor. Within 10 min all HPMA copolymers accumulated effectively in the tumor regardless of MW (1.0–1.5% of injected dose per g of tumor). However, higher MW copolymers (>50 K) showed significantly increased tumor accumulation after 6 h, while the lower MW copolymers (<40 K) were cleared rapidly from tumor tissue due to rapid diffusion back into the bloodstream. Blood clearance was also MW‐dependent; the lower MW copolymers displayed rapid clearance, with kidney radioactivity of the copolymers of MW <20 K representing 24% of injected dose per g kidney at 1 min after i.v. administration. Within 10 min these copolymers passed through the kidney and were excreted in the urine. Higher MW copolymers consistently showed kidney levels of 3–5% dose per g kidney in the early phase with no time‐dependent accumulation in kidney. There was also no progressive accumulation in muscle or liver, regardless of polymer MW. These results suggest the “EPR effect” in solid tumor primarily arises from in the difference in clearance rate between the solid tumor and the normal tissues after initial penetration of the polymers into these tissues. Blackwell Publishing Ltd 1998-03 /pmc/articles/PMC5921799/ /pubmed/9600125 http://dx.doi.org/10.1111/j.1349-7006.1998.tb00563.x Text en |
spellingShingle | Article Noguchi, Youichiro Wu, Jun Duncan, Ruth Strohalm, Jiří Ulbrich, Karel Akaike, Takaaki Maeda, Hiroshi Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues |
title | Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues |
title_full | Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues |
title_fullStr | Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues |
title_full_unstemmed | Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues |
title_short | Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues |
title_sort | early phase tumor accumulation of macromolecules: a great difference in clearance rate between tumor and normal tissues |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921799/ https://www.ncbi.nlm.nih.gov/pubmed/9600125 http://dx.doi.org/10.1111/j.1349-7006.1998.tb00563.x |
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