Magnetic resonance Imaging - Measured blood flow change after antiangiogenic therapy with PTK787/ZK 222584 correlates with clinical outcome in metastatic renal cell carcinoma

Purpose: To measure changes in tumor blood flow following treatment with PTK787/ZK 222584, a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, and their association with clinical response in patients with metastatic renal cell carcinoma. Experimental Design: In 10 patients with metastatic renal cell carcinoma treated with PTK787/ ZK 222584, tumor blood flow was evaluated by arterial spin labeling (ASL) magnetic resonance imaging before and 1 month on treatment. Changes in blood flow after 1 month of treatment were compared with bidimensional tumor response at 4 months of treatment using the Mann- Whitney test. Results: Changes in blood flow at 1 month and changes in tumor size measured at 4 months or at time of disease progression were significantly correlated (P = 0.01). Patients with progressive disease within 4 months on treatment (n = 4) had a nonsignificant increase in tumor blood flow at 1 month (+25 ± 33%; P = 0.43), whereas patients with stable disease or partial response at 4 months (n = 6) had a significant decrease in tumor blood flow at 1 month (-42 ± 22%; P = 0.02). Conclusion:These results suggest that decreasing tumor blood flow with PTK787/ZK 222584 therapy, as shown as soon as 1 month on therapy by ASL, may predict for a favorable clinical outcome. These data are consistent with a hypothetical functional role for tumor ischemia in the mechanism of response to anti-vascular endothelial growth factor therapy. ASL blood flow magnetic resonance imaging shows promise as an early predictor of clinical response to antiangiogenic therapies.