Abstract P5-01-09: Evaluation of Tumor Blood Flow with Dynamic 18F-Fluorodeoxyglucose Positron Emission Tomography: Correlation with Microvessel Density

Abstract

Abstract Background: Breast cancer is typically associated with an increase in tumor blood flow (due to angiogenesis) and tumor metabolism. Thus, these 2 key parameters are essential to characterize aggressiveness of breast tumors. Moreover, angiogenesis is a potential target for specific therapies. Positron Emission Tomography (PET) with 18F-Fluorodeoxyglucose (FDG) has become the gold standard for in vivo evaluation of tumor metabolism. A method for simultaneous measurement of blood flow and metabolism from a single injection of FDG may be an important addition for functional imaging of breast tumors. Unfortunately, there is no consensus on the validity of dynamic FDG acquisition for the evaluation of tumor blood flow. Objective: to compare a new technique for simultaneous evaluation of tumor blood flow and metabolism, using a dynamic acquisition of FDG PET, with proliferation and endothelial cell markers. Material and methods: Twenty-eight patients with new diagnosed locally advanced breast cancer were included. In addition to diagnosis and tumor grading, biopsy samples of each tumor were used to assess the Ki-67 index of proliferation and the immuno-staining for CD31 (a panendothelial cell marker) and CD105 (a proliferation-related endothelial cell marker) (both expressed as number of labeled vessels counted on 10 consecutive high power fields, 400X magnification). All patients underwent FDG PET at least one week after sample biopsy and before any treatment. Dynamic 2 minutes acquisition was performed immediately after intravenous injection of 5 MBq/Kg of FDG; tumor Blood Flow (BF, in ml/min/g) was then calculated using a single compartiment kinetic model. Static acquisition was performed 60 minutes after injection for quantification of delayed FDG tumor uptake (“Standardized Uptake Value”, SUV), reflecting tumor metabolism. Results: Pathologic and PET data were available for all patients. The SUV measured on delayed PET images was strongly positively correlated with the expression of Ki-67 (r=+0.693; P<0.0001). In contrast, there was no significant correlation between SUV and endothelial markers (CD31 and CD105). Tumor BF was positively correlated with the expression of CD31 (r=+0.392; p=0.039) and CD105 (r=+0.470; p=0.016). In contrast, there was no significant correlation between BF and Ki-67. Patients were categorized according to low (inframedian) or high (supramedian) tumor BF. Patients with high tumor BF showed a higher mean CD31 expression (236±169 vs 124±47, p=0.025) and a higher mean CD105 expression (110±73 vs 51±14; p=0.006) when compared with low tumor BF. In contrast there was no significant difference concerning SUV and Ki-67. Conclusion: Tumor BF quantified by dynamic FDG PET is related to tumor microvessel density evaluated by immunohistochemistry. Thus, dynamic FDG PET is a valuable tool to evaluate both tumor blood flow and metabolism. Further investigations are needed to confirm the respective role of these 2 key parameters for elaboration of therapeutic strategies and response assessment in locally advanced breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-09.