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01-02-2012 | PRECLINICAL STUDIES

Combining functional imaging and interstitial pressure measurements to evaluate two anti-angiogenic treatments

Authors: Ingrid Leguerney, Nathalie Lassau, Serge Koscielny, Mélanie Rodrigues, Christophe Massard, Valérie Rouffiac, Baya Benatsou, Jessie Thalmensi, Olivia Bawa, Paule Opolon, Pierre Peronneau, Alain Roche

Published in: Investigational New Drugs | Issue 1/2012

Summary

Background: Interstitial hypertension is responsible for poor capillary blood flow and hampered drug delivery. The efficacy of combined sorafenib/bevacizumab treatment given according to different administration schedules has been evaluated by measuring both interstitial pressure (IP) and quantitative dynamic contrast-enhanced ultrasonography (DCE-US) parameters in melanoma-bearing mice. Materiel and Methods: Sixty mice were xenografted with B16F10 melanoma. Animals received a daily administration over 4 days (D0 to D3) of either sorafenib at 30 mg/kg, bevacizumab at 2.5 mg/kg alone, or different schedules of combined treatments. Perfusion parameters determined using an Aplio® sonograph (Toshiba) with SonoVue® contrast agent (Bracco) were compared to IP measurements using fiberoptic probes (Samba®) at D0, D2, D4, D8. Results: The mean baseline IP values ranged between 6.55 and 31.29 mmHg in all the groups. A transient IP decrease occurred at D2 in all treated groups, and especially in the concomitant group which exhibited a significant IP reduction compared to D0. A significant decrease in both the peak intensity and the area under the curve was observed at D4 in the group with concomitant administration of both molecules which yielded maximal inhibition of the tumor volume and the number of vessels. No correlation was found between IP values and volume or perfusion parameters, indicating complex relationships between IP and vascularization. No IP gradients were found between the center and the periphery but IP values in these two regions were significantly correlated (R = 0.93). Conclusion: The results suggest that IP variations could be predictive of vascular changes and that one single IP measurement is sufficient to fully characterize the whole tumor.

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Title: Combining functional imaging and interstitial pressure measurements to evaluate two anti-angiogenic treatments
Authors: Ingrid Leguerney
Nathalie Lassau
Serge Koscielny
Mélanie Rodrigues
Christophe Massard
Valérie Rouffiac
Baya Benatsou
Jessie Thalmensi
Olivia Bawa
Paule Opolon
Pierre Peronneau
Alain Roche
Publication date: 01-02-2012
Publisher: Springer US
Published in: Investigational New Drugs / Issue 1/2012
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-010-9543-y

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