Blood flow and Vd (water): both biomarkers required for interpreting the effects of vascular targeting agents on tumor and normal tissue.

2.50
Hdl Handle:
http://hdl.handle.net/10541/69701
Title:
Blood flow and Vd (water): both biomarkers required for interpreting the effects of vascular targeting agents on tumor and normal tissue.
Authors:
Kötz, Barbara; West, Catharine M L; Saleem, Azeem; Jones, Terry; Price, Patricia M
Abstract:
Positron emission tomography studies with oxygen-15-labeled water provide in vivo quantitative tissue perfusion variables-blood flow and fractional volume of distribution of water [V(d) (water)]. To investigate the relationship between perfusion variables and the effect of vascular-targeting agents on vasculature, we measured tissue perfusion in tumors, spleen, kidney, and liver before and after treatment with combretastatin-A4-phosphate, a combination of nicotinamide and carbogen (N/C), and interferon (IFN). We observed that mean tumor blood flow and V(d) (water) was lower than in kidney, liver, and spleen at baseline. Blood flow and V(d) (water) were related in tumor (r = 0.62; P = 0.004) at baseline, but not in other normal tissues evaluated, where minimal variations in V(d) (water) were observed over a wide range of blood flow. Despite the relationship between blood flow and V(d) (water) in tumors before intervention, vascular-targeting agent-induced changes in these perfusion variables were not correlated. In contrast, changes in blood flow and V(d) (water) correlated in kidney and spleen after N/C and in kidney after combretastatin-A4-phosphate. The close relation between blood flow and V(d) (water) in tumors but not normal tissue may reflect barriers to fluid exchange in tumors because of necrosis and/or increased interstitial fluid pressure and underlies the importance and interdependence of these positron emission tomography perfusion variables under these conditions. As blood flow and V(d) (water) signify different aspects of tissue perfusion, the differential effects of interventions on both variables, flow and V(d) (water), should therefore be reported in future studies.
Affiliation:
Academic Department of Radiation Oncology, The University of Manchester, Manchester, UK.
Citation:
Blood flow and Vd (water): both biomarkers required for interpreting the effects of vascular targeting agents on tumor and normal tissue. 2009, 8 (2):303-9 Mol. Cancer Ther.
Journal:
Molecular Cancer Therapeutics
Issue Date:
Feb-2009
URI:
http://hdl.handle.net/10541/69701
DOI:
10.1158/1535-7163.MCT-08-1016
PubMed ID:
19208824
Type:
Article
Language:
en
ISSN:
1535-7163
Appears in Collections:
All Christie Publications ; Academic Department of Radiation Oncology - ADRO

Full metadata record

DC FieldValue Language
dc.contributor.authorKötz, Barbara-
dc.contributor.authorWest, Catharine M L-
dc.contributor.authorSaleem, Azeem-
dc.contributor.authorJones, Terry-
dc.contributor.authorPrice, Patricia M-
dc.date.accessioned2009-06-04T14:39:06Z-
dc.date.available2009-06-04T14:39:06Z-
dc.date.issued2009-02-
dc.identifier.citationBlood flow and Vd (water): both biomarkers required for interpreting the effects of vascular targeting agents on tumor and normal tissue. 2009, 8 (2):303-9 Mol. Cancer Ther.en
dc.identifier.issn1535-7163-
dc.identifier.pmid19208824-
dc.identifier.doi10.1158/1535-7163.MCT-08-1016-
dc.identifier.urihttp://hdl.handle.net/10541/69701-
dc.description.abstractPositron emission tomography studies with oxygen-15-labeled water provide in vivo quantitative tissue perfusion variables-blood flow and fractional volume of distribution of water [V(d) (water)]. To investigate the relationship between perfusion variables and the effect of vascular-targeting agents on vasculature, we measured tissue perfusion in tumors, spleen, kidney, and liver before and after treatment with combretastatin-A4-phosphate, a combination of nicotinamide and carbogen (N/C), and interferon (IFN). We observed that mean tumor blood flow and V(d) (water) was lower than in kidney, liver, and spleen at baseline. Blood flow and V(d) (water) were related in tumor (r = 0.62; P = 0.004) at baseline, but not in other normal tissues evaluated, where minimal variations in V(d) (water) were observed over a wide range of blood flow. Despite the relationship between blood flow and V(d) (water) in tumors before intervention, vascular-targeting agent-induced changes in these perfusion variables were not correlated. In contrast, changes in blood flow and V(d) (water) correlated in kidney and spleen after N/C and in kidney after combretastatin-A4-phosphate. The close relation between blood flow and V(d) (water) in tumors but not normal tissue may reflect barriers to fluid exchange in tumors because of necrosis and/or increased interstitial fluid pressure and underlies the importance and interdependence of these positron emission tomography perfusion variables under these conditions. As blood flow and V(d) (water) signify different aspects of tissue perfusion, the differential effects of interventions on both variables, flow and V(d) (water), should therefore be reported in future studies.en
dc.language.isoenen
dc.subjectCanceren
dc.subjectTumour Markersen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshCarbon Dioxide-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasms-
dc.subject.meshNiacinamide-
dc.subject.meshOrgan Specificity-
dc.subject.meshOxygen-
dc.subject.meshRegional Blood Flow-
dc.subject.meshTumor Markers, Biological-
dc.subject.meshWater-
dc.titleBlood flow and Vd (water): both biomarkers required for interpreting the effects of vascular targeting agents on tumor and normal tissue.en
dc.typeArticleen
dc.contributor.departmentAcademic Department of Radiation Oncology, The University of Manchester, Manchester, UK.en
dc.identifier.journalMolecular Cancer Therapeuticsen

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