Magnetic Resonance Imaging–Measured Blood Flow Change after Antiangiogenic Therapy with PTK787/ZK 222584 Correlates with Clinical Outcome in Metastatic Renal Cell Carcinoma

Abstract

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. 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. 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). 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.