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Positron Emission Tomography Based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer Using Copper-64 Liposomes

Hansen, Anders E. ; Petersen, Anncatrine L. ; Henriksen, Jonas R. ; Boerresen, Betina ; Rasmussen, Palle ; Elema, Dennis R. ; Rosenschöld, Per Munck Af LU orcid ; Kristensen, Annemarie T. ; Kjær, Andreas and Andresen, Thomas L. (2015) In ACS Nano 9(7). p.6985-6995
Abstract

Since the first report of the enhanced permeability and retention (EPR) effect, the research in nanocarrier based antitumor drugs has been intense. The field has been devoted to treatment of cancer by exploiting EPR-based accumulation of nanocarriers in solid tumors, which for many years was considered to be a ubiquitous phenomenon. However, the understanding of differences in the EPR-effect between tumor types, heterogeneities within each patient group, and dependency on tumor development stage in humans is sparse. It is therefore important to enhance our understanding of the EPR-effect in large animals and humans with spontaneously developed cancer. In the present paper, we describe a novel loading method of copper-64 into PEGylated... (More)

Since the first report of the enhanced permeability and retention (EPR) effect, the research in nanocarrier based antitumor drugs has been intense. The field has been devoted to treatment of cancer by exploiting EPR-based accumulation of nanocarriers in solid tumors, which for many years was considered to be a ubiquitous phenomenon. However, the understanding of differences in the EPR-effect between tumor types, heterogeneities within each patient group, and dependency on tumor development stage in humans is sparse. It is therefore important to enhance our understanding of the EPR-effect in large animals and humans with spontaneously developed cancer. In the present paper, we describe a novel loading method of copper-64 into PEGylated liposomes and use these liposomes to evaluate the EPR-effect in 11 canine cancer patients with spontaneous solid tumors by PET/CT imaging. We thereby provide the first high-resolution analysis of EPR-based tumor accumulation in large animals. We find that the EPR-effect is strong in some tumor types but cannot be considered a general feature of solid malignant tumors since we observed a high degree of accumulation heterogeneity between tumors. Six of seven included carcinomas displayed high uptake levels of liposomes, whereas one of four sarcomas displayed signs of liposome retention. We conclude that nanocarrier-radiotracers could be important in identifying cancer patients that will benefit from nanocarrier-based therapeutics in clinical practice.

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author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cancer, drug delivery, EPR-effect, imaging, liposomes, nanomedicine, nanoparticles
in
ACS Nano
volume
9
issue
7
pages
6985 - 6995
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:26022907
  • scopus:84934337555
ISSN
1936-0851
DOI
10.1021/acsnano.5b01324
language
English
LU publication?
no
additional info
Publisher Copyright: © 2015 American Chemical Society.
id
106d9f90-5cd3-4141-89b5-a44bebe31b23
date added to LUP
2023-07-31 13:36:53
date last changed
2024-04-20 01:03:27
@article{106d9f90-5cd3-4141-89b5-a44bebe31b23,
  abstract     = {{<p>Since the first report of the enhanced permeability and retention (EPR) effect, the research in nanocarrier based antitumor drugs has been intense. The field has been devoted to treatment of cancer by exploiting EPR-based accumulation of nanocarriers in solid tumors, which for many years was considered to be a ubiquitous phenomenon. However, the understanding of differences in the EPR-effect between tumor types, heterogeneities within each patient group, and dependency on tumor development stage in humans is sparse. It is therefore important to enhance our understanding of the EPR-effect in large animals and humans with spontaneously developed cancer. In the present paper, we describe a novel loading method of copper-64 into PEGylated liposomes and use these liposomes to evaluate the EPR-effect in 11 canine cancer patients with spontaneous solid tumors by PET/CT imaging. We thereby provide the first high-resolution analysis of EPR-based tumor accumulation in large animals. We find that the EPR-effect is strong in some tumor types but cannot be considered a general feature of solid malignant tumors since we observed a high degree of accumulation heterogeneity between tumors. Six of seven included carcinomas displayed high uptake levels of liposomes, whereas one of four sarcomas displayed signs of liposome retention. We conclude that nanocarrier-radiotracers could be important in identifying cancer patients that will benefit from nanocarrier-based therapeutics in clinical practice.</p>}},
  author       = {{Hansen, Anders E. and Petersen, Anncatrine L. and Henriksen, Jonas R. and Boerresen, Betina and Rasmussen, Palle and Elema, Dennis R. and Rosenschöld, Per Munck Af and Kristensen, Annemarie T. and Kjær, Andreas and Andresen, Thomas L.}},
  issn         = {{1936-0851}},
  keywords     = {{cancer; drug delivery; EPR-effect; imaging; liposomes; nanomedicine; nanoparticles}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{6985--6995}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Nano}},
  title        = {{Positron Emission Tomography Based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer Using Copper-64 Liposomes}},
  url          = {{http://dx.doi.org/10.1021/acsnano.5b01324}},
  doi          = {{10.1021/acsnano.5b01324}},
  volume       = {{9}},
  year         = {{2015}},
}