Macromolecular contrast agents help stage tumors

Radiologists are interested in characterizing the nature and permeability of blood vessels in patients with cancer because this information has many uses: to differentiate benign lesions from malignant ones, relate prognosis and treatment strategies to the specific biological features of a patient's tumors, determine the angiogenesis status of a tumor, and grade tumors noninvasively.

Imaging data on individual tumors also may assess a patient's response to anti-angiogenesis drugs as well as other forms of cancer treatment without waiting six or eight weeks.

"It's possible that a patient could start treatment one day and be sent to us for imaging the next day or even hours later, and we could say this drug works in this patient or this drug doesn't work," said Dr. Robert C. Brasch, a professor of radiology at the University of California, San Francisco.

During the Marie Curie Honorary Lecture, Brasch predicted that macromolecular MR imaging tracers will soon be able to flag the existence of tumor microvessels by tracking the leakage of contrast from blood vessels into the interstitia over time. Macromolecular contrast agents also create different patterns of enhancement for tumor grades, enhancing constantly in benign tumors and gradually accumulating in malignant cancers.

Dextran-coated ultrasmall supraparamagnetic iron oxide particles are another vehicle for depicting abnormal permeability and differentiating benign from malignant tumors. Pixel by pixel maps from the first clinical trial of these particles conducted in Europe showed that abnormal permeability increased with tumor grade.

MRI assessments of permeability not only correlate highly with histologic determinations of angiogenesis, they also indicate the effectiveness of anti-angiogenesis treatment. In one study of an antibody directed against vascular endothelial growth factor (VEGF), the substance that stimulates tumor angiogenesis, MR showed that permeability declined between 60% and 70% along the rim, in the center, and across the whole tumor. MR revealed significant declines in permeability within an hour after only one dose of the antibody.

MR also demonstrates the effect that anti-angiogenesis drugs exert on the action of standard chemotherapeutic agents. In one study, permeability dropped by more than half after an anti-angiogenesis drug was administered to tumors that had been treated with cisplatin, but it was not affected in tumours previously treated with 5-fluorouracil.

The development of macromolecular contrast agents for MR could create considerably more business for radiologists.

"We could do more and better for cancer patients. We might even provide a rational basis for timing of combination therapy," Brasch said.