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  • 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.
  • 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. (en)
Title
  • Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging
  • Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging (en)
skos:prefLabel
  • Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging
  • Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging (en)
skos:notation
  • RIV/61389013:_____/14:00427396!RIV15-GA0-61389013
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(GCP207/12/J030)
http://linked.open...iv/cisloPeriodika
  • 28 May
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 6994
http://linked.open...ai/riv/idVysledku
  • RIV/61389013:_____/14:00427396
http://linked.open...riv/jazykVysledku
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  • drug targeting; nanomedicine; theranostics (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • NL - Nizozemsko
http://linked.open...ontrolniKodProRIV
  • [D7A6E1396D27]
http://linked.open...i/riv/nazevZdroje
  • Journal of Controlled Release
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 182
http://linked.open...iv/tvurceVysledku
  • Pechar, Michal
  • Pola, Robert
  • Lammers, T.
  • Kiessling, F.
  • Kunjachan, S.
  • Storm, G.
  • Theek, B.
  • Gremse, F.
  • Ehling, J.
  • Deckers, R.
  • Fokong, S.
http://linked.open...ain/vavai/riv/wos
  • 000335554000009
issn
  • 0168-3659
number of pages
http://bibframe.org/vocab/doi
  • 10.1016/j.jconrel.2014.03.007
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