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

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 vasculartargeting 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 agentinduced 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. [Mol Cancer Ther 2009;8(2):303 -9]

Molecular Imaging of Aquaglycero-Aquaporins: Its Potential for Cancer Characterization

“…30,31) In conclusion, based on the present study we propose that radiolabeled glycerol could be used as a molecular probe targeting agAQPs. This might enable the estimation of agAQP expression by comparing radioactivity in the tissue of interest and plasma in the same individual, thus providing valuable information about the characteristics of the tissue.…”

Positron emission tomography imaging approaches for external beam radiation therapies: current status and future developments

“…For example, recent PET research on liver metastases using 15 O-radiolabelled water has shown that those with higher plasma tissue perfusion variables (i.e. improved blood flow or perfusion) were associated with better patient RT outcome and improved survival [63][64][65]. This suggests that assessment of indicators of tumour perfusion, such as exchangeable tissue volume of distribution using PET, may be useful as BTV markers.…”

Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

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