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

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.

• Authors: Benjamin Theek, Felix Gremse, Sijumon Kunjachan, Stanley Fokong, Robert Pola, Michal Pechar, Roel Deckers, Gert Storm, Josef Ehling, Fabian Kiessling, Twan Lammers
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 182 Pg. 83-9 (May 28 2014) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 24631862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Acrylamides
• Contrast Media
• Enbucrilate

Topics

• Acrylamides (administration & dosage)
• Animals
• Blood Volume
• Cell Line, Tumor
• Contrast Media (administration & dosage)
• Drug Delivery Systems
• Enbucrilate
• Mice, Nude
• Microbubbles
• Neoplasms (blood supply, diagnostic imaging, metabolism, physiopathology)
• Permeability
• Regional Blood Flow
• Tomography (methods)
• Ultrasonography