Document Detail

Combining functional imaging and interstitial pressure measurements to evaluate two anti-angiogenic treatments.
MedLine Citation:
PMID:  20924644     Owner:  NLM     Status:  MEDLINE    
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.
MATERIAL AND METHODS: [corrected] 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.
Ingrid Leguerney; Nathalie Lassau; Serge Koscielny; Mélanie Rodrigues; Christophe Massard; Valérie Rouffiac; Baya Benatsou; Jessie Thalmensi; Olivia Bawa; Paule Opolon; Pierre Peronneau; Alain Roche
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Publication Detail:
Type:  Journal Article     Date:  2010-10-06
Journal Detail:
Title:  Investigational new drugs     Volume:  30     ISSN:  1573-0646     ISO Abbreviation:  Invest New Drugs     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-12     Completed Date:  2012-05-08     Revised Date:  2014-10-20    
Medline Journal Info:
Nlm Unique ID:  8309330     Medline TA:  Invest New Drugs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  144-56     Citation Subset:  IM    
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MeSH Terms
Angiogenesis Inhibitors / administration & dosage*
Antibodies, Monoclonal, Humanized / administration & dosage*
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Benzenesulfonates / administration & dosage*
Contrast Media / diagnostic use
Drug Administration Schedule
Extracellular Fluid / metabolism*
Fiber Optic Technology
Melanoma, Experimental / blood supply,  drug therapy*,  metabolism,  pathology,  ultrasonography
Neovascularization, Pathologic / metabolism,  prevention & control*,  ultrasonography
Niacinamide / analogs & derivatives
Perfusion Imaging* / methods
Phenylurea Compounds
Phospholipids / diagnostic use
Pyridines / administration & dosage*
Regional Blood Flow
Sulfur Hexafluoride / diagnostic use
Time Factors
Transducers, Pressure
Ultrasonography, Doppler
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal, Humanized; 0/Benzenesulfonates; 0/Contrast Media; 0/Phenylurea Compounds; 0/Phospholipids; 0/Pyridines; 0/contrast agent BR1; 0/sorafenib; 25X51I8RD4/Niacinamide; 2S9ZZM9Q9V/bevacizumab; WS7LR3I1D6/Sulfur Hexafluoride

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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