Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 83-89 |
| Number of pages | 7 |
| Journal | Journal of controlled release |
| Volume | 182 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- METIS-309155
- IR-95133
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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 journal › Article › Academic › peer-review
TY - JOUR
T1 - Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging
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
N1 - article
PY - 2014
Y1 - 2014
N2 - 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.
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.
KW - METIS-309155
KW - IR-95133
U2 - 10.1016/j.jconrel.2014.03.007
DO - 10.1016/j.jconrel.2014.03.007
M3 - Article
VL - 182
SP - 83
EP - 89
JO - Journal of controlled release
JF - Journal of controlled release
SN - 0168-3659
ER -