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

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 q...

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Bibliographic Details
Published in:Investigational new drugs 2012-02, Vol.30 (1), p.144-156
Main Authors: Leguerney, Ingrid, Lassau, Nathalie, Koscielny, Serge, Rodrigues, Mélanie, Massard, Christophe, Rouffiac, Valérie, Benatsou, Baya, Thalmensi, Jessie, Bawa, Olivia, Opolon, Paule, Peronneau, Pierre, Roche, Alain
Format: Article
Language:English
Subjects:
Angiogenesis
Angiogenesis Inhibitors - administration & dosage
Animals
Antibodies, Monoclonal, Humanized - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Benzenesulfonates - administration & dosage
Bevacizumab
Blood pressure
Cancer therapies
Contrast Media
Diagnostic tests
Drug Administration Schedule
Drug dosages
Experiments
Extracellular Fluid - metabolism
Female
Fiber Optic Technology
Medicine
Medicine & Public Health
Melanoma
Melanoma, Experimental - blood supply
Melanoma, Experimental - diagnostic imaging
Melanoma, Experimental - drug therapy
Melanoma, Experimental - metabolism
Melanoma, Experimental - pathology
Mice
Neovascularization, Pathologic - diagnostic imaging
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - prevention & control
Niacinamide - analogs & derivatives
Oncology
Perfusion Imaging - methods
Pharmacology
Pharmacology/Toxicology
Phenylurea Compounds
Phospholipids
Preclinical Studies
Pressure
Pyridines - administration & dosage
Regional Blood Flow
Studies
Sulfur Hexafluoride
Time Factors
Transducers, Pressure
Tumors
Ultrasonic imaging
Ultrasonography, Doppler
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Summary: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.
ISSN:0167-6997
1573-0646
DOI:10.1007/s10637-010-9543-y