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

Anders Elias Hansen, Anncatrine Luisa Petersen, Jonas Rosager Henriksen, Betina Børresen, Palle Rasmussen, Dennis Ringkjøbing Elema, Per Munck af Rosenschöld, Annemarie T. Kristensen, Andreas Kjær, Thomas Lars Andresen

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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 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.
Original languageEnglish
JournalA C S Nano
Volume9
Issue number7
Pages (from-to)6985–6995
Number of pages11
ISSN1936-0851
DOIs
Publication statusPublished - 2015

Keywords

  • Nanomedicine
  • Cancer
  • EPR-effect
  • Drug delivery
  • Imaging
  • Nanoparticles
  • Liposomes

Cite this

Hansen, Anders Elias ; Petersen, Anncatrine Luisa ; Henriksen, Jonas Rosager ; Børresen, Betina ; Rasmussen, Palle ; Elema, Dennis Ringkjøbing ; Rosenschöld, Per Munck af ; Kristensen, Annemarie T. ; Kjær, Andreas ; Andresen, Thomas Lars. / Positron Emission Tomography Based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer Using Copper-64 Liposomes. In: A C S Nano. 2015 ; Vol. 9, No. 7. pp. 6985–6995.
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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 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.",
keywords = "Nanomedicine, Cancer, EPR-effect, Drug delivery, Imaging, Nanoparticles, Liposomes",
author = "Hansen, {Anders Elias} and Petersen, {Anncatrine Luisa} and Henriksen, {Jonas Rosager} and Betina B{\o}rresen and Palle Rasmussen and Elema, {Dennis Ringkj{\o}bing} and Rosensch{\"o}ld, {Per Munck af} and Kristensen, {Annemarie T.} and Andreas Kj{\ae}r and Andresen, {Thomas Lars}",
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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 Elias; Petersen, Anncatrine Luisa; Henriksen, Jonas Rosager; Børresen, Betina; Rasmussen, Palle; Elema, Dennis Ringkjøbing; Rosenschöld, Per Munck af; Kristensen, Annemarie T.; Kjær, Andreas; Andresen, Thomas Lars.

In: A C S Nano, Vol. 9, No. 7, 2015, p. 6985–6995.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - Positron Emission Tomography Based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer Using Copper-64 Liposomes

AU - Hansen, Anders Elias

AU - Petersen, Anncatrine Luisa

AU - Henriksen, Jonas Rosager

AU - Børresen, Betina

AU - Rasmussen, Palle

AU - Elema, Dennis Ringkjøbing

AU - Rosenschöld, Per Munck af

AU - Kristensen, Annemarie T.

AU - Kjær, Andreas

AU - Andresen, Thomas Lars

PY - 2015

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N2 - 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.

AB - 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.

KW - Nanomedicine

KW - Cancer

KW - EPR-effect

KW - Drug delivery

KW - Imaging

KW - Nanoparticles

KW - Liposomes

U2 - 10.1021/acsnano.5b01324

DO - 10.1021/acsnano.5b01324

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SP - 6985

EP - 6995

JO - A C S Nano

JF - A C S Nano

SN - 1936-0851

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ER -