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

Clin Cancer Res. 2008 Sep 1;14(17):5548-54. doi: 10.1158/1078-0432.CCR-08-0417.


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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Renal Cell / blood supply*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Disease Progression
  • Feasibility Studies
  • Humans
  • Kidney Neoplasms / blood supply*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Magnetic Resonance Imaging / methods*
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / drug therapy
  • Phthalazines / therapeutic use*
  • Pyridines / therapeutic use*
  • Regional Blood Flow / drug effects


  • Angiogenesis Inhibitors
  • Phthalazines
  • Pyridines
  • vatalanib