Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging

Benjamin Theek, Felix Gremse, Sijumon Kunjachan, Stanley Fokong, Robert Pola, Michal Pechar, Roel Deckers, Gert Storm, Josef Ehling, Fabian Kiessling, Twan Lammers

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~ 10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~ 0.8 and p-values of < 0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments.
Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalJournal of controlled release
Volume182
DOIs
Publication statusPublished - 2014

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Drug Delivery Systems
Permeability
Ultrasonography
Tomography
Neoplasms
Fluorescence
Drug Carriers
Nanomedicine
Optical Imaging

Keywords

  • METIS-309155
  • IR-95133

Cite this

Theek, Benjamin ; Gremse, Felix ; Kunjachan, Sijumon ; Fokong, Stanley ; Pola, Robert ; Pechar, Michal ; Deckers, Roel ; Storm, Gert ; Ehling, Josef ; Kiessling, Fabian ; Lammers, Twan. / Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging. In: Journal of controlled release. 2014 ; Vol. 182. pp. 83-89.
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abstract = "The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~ 10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12{\%} of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11{\%}. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~ 0.8 and p-values of < 0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments.",
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Theek, B, Gremse, F, Kunjachan, S, Fokong, S, Pola, R, Pechar, M, Deckers, R, Storm, G, Ehling, J, Kiessling, F & Lammers, T 2014, 'Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging' Journal of controlled release, vol. 182, pp. 83-89. https://doi.org/10.1016/j.jconrel.2014.03.007

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging. / Theek, Benjamin; Gremse, Felix; Kunjachan, Sijumon; Fokong, Stanley; Pola, Robert; Pechar, Michal; Deckers, Roel; Storm, Gert; Ehling, Josef; Kiessling, Fabian; Lammers, Twan.

In: Journal of controlled release, Vol. 182, 2014, p. 83-89.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Theek, Benjamin

AU - Gremse, Felix

AU - Kunjachan, Sijumon

AU - Fokong, Stanley

AU - Pola, Robert

AU - Pechar, Michal

AU - Deckers, Roel

AU - Storm, Gert

AU - Ehling, Josef

AU - Kiessling, Fabian

AU - Lammers, Twan

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AB - The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~ 10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~ 0.8 and p-values of < 0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments.

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DO - 10.1016/j.jconrel.2014.03.007

M3 - Article

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SP - 83

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JO - Journal of controlled release

JF - Journal of controlled release

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