The purpose of this study was to prospectively evaluate the relationship between tumor blood flow and glucose metabolism as evaluated by dynamic first-pass 18 F-FDG PET and by proliferation and endothelial pathologic markers in the setting of newly diagnosed breast cancer. Methods: Forty patients were prospectively included. Biopsy samples of each tumor were used to assess the Ki67 index of proliferation and immunostaining for CD34 (a panendothelial cell marker) and CD105 (a proliferation-related endothelial cell marker). All patients underwent 18 F-FDG PET/CT at least 1 wk after sample biopsy and before any treatment. A dynamic 2-min acquisition was performed immediately after intravenous injection of a 5 MBq/kg dose of 18 F-FDG; tumor blood flow was then calculated using a singlecompartment kinetic model. A static acquisition was performed 90 min after injection for quantification of delayed 18 F-FDG tumor uptake (standardized uptake value maximal index [SUV max ]), reflecting tumor metabolism. Results: Pathologic and PET/ CT data were available for all patients. The SUV max measured on delayed PET images correlated strongly and positively with the expression of Ki67 (r 5 10.69; P , 0.0001). In contrast, there was no significant correlation between SUV max and endothelial markers (CD34 and CD105). Tumor blood flow correlated positively with the expression of CD34 and CD105 (P 5 0.016 and P 5 0.007, respectively) and with the expression of Ki67 (P 5 0.028). By logistic regression analysis, only expression of Ki67 remained an independent predictor of high (supramedian) SUV max ; CD105 score and histopathologic grade 3 were independently associated with a high (supramedian) tumor blood flow level. Conclusion: Tumor blood flow quantified by dynamic first-pass 18 F-FDG PET/CT is significantly associated with tumor angiogenesis as evaluated by immunohistochemistry in the setting of breast cancer, whereas tumor metabolism appears to be more associated with markers of proliferation. Thus, determination of tumor blood flow and metabolism with a single injection of 18 F-FDG could be an exciting alternative to more complex and less available techniques. Breast cancer is the most commonly diagnosed cancer in women and is the primary cause of death by cancer for women in the western world. Because of the Warburg effect (1), breast tumors are typically associated with an increase in tumor blood flow due to angiogenesis and an increase in glucose metabolism, but glucose metabolism and blood flow are often mismatched in breast cancer (2). Moreover, a flow-metabolism mismatch (high glucose metabolism relative to blood flow) is associated with poor response to systemic therapy and early relapse or disease progression (3,4). Thus, determination of these 2 key parameters is essential in characterizing the aggressiveness of breast tumors.PET/CT with 18 F-FDG is the gold standard for in vivo evaluation of tumor glucose metabolism and is widely used in clinical oncology. In the setting of breast cancer, 18 F-FDG uptake has also been...
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