In vivo monitoring of tumor angiogenesis with MR imaging.

Magnetic resonance (MR) imaging is a widely employed diagnostic method for the evaluation of patients with tumors. This method is noted for its remarkable soft-tissue definition, absence of ionizing radiation, high spatial and temporal resolution, and ability to generate images in any plane of the entire body. Equipment costs and, thus, examination costs are relatively high, however. MR imaging has been proposed and tested, both experimentally and clinically, as a method to characterize tumors regarding their state of angiogenesis. Multiple approaches to the challenge of MR imaging assays of angiogenesis have been proposed, some of which are potentially additive; all are intended to provide information regarding tumor microvessels. The quantitative end points that are sought include tissue plasma/blood volume, transendothelial permeability to water or solutes, perfusion/flow, and relative concentration of angiogenesis-specific molecules. The available approaches can be divided into intrinsic (non-contrast material enhanced) and contrast material-enhanced methods. The latter methods can be further divided by the type of contrast medium employed: small molecular agents that distribute rapidly in the extracellular space (so-called nonspecific or extracellular-fluid-space [ECF] agents), large molecular agents designed for prolonged intravascular retention (socalled macromolecular contrast media [MMCM] or bloodpool agents), and targeted agents intended to accumulate at the sites of concentrated angiogenesis mediator. Today, ECF contrast agents are commercially available and being used in clinical evaluations of antiangiogenesis drug treatments. Macromolecular contrast media are currently in clinical trials, but they are not now approved for use in humans. Molecular-targeted contrast media are in preclinical development. This section summarizes some of the many reports dealing with MR imaging assays of angiogenesis. For clarity, the discussion is divided by the specific MR imaging approach used. The rationale for that approach, limited information regarding the technique itself, accumulated experience, and limitations are provided, as well.