Contrast agents and applications to assess tumor angiogenesis in vivo by magnetic resonance imaging

Angiogenesis plays a key role in the development of cancer and is precondition for tumor growth, invasion and spread. Therefore, numerous angiogenesis inhibitors have been developed, of which some show potential to defeat cancer in preclinical and clinical trials. However, response to antiangiogenic treatments is often delayed and marked by high interindividual variability making a closely mashed and efficient observation of the patient necessary. Therefore, surrogate markers which specifically catch early response to tumor therapy are highly desirable. Functional parameters like relative blood volume, perfusion and vessel permeability can be assessed using T(1) and T(2)*-weighted dynamic contrast-enhanced (DCE) MRI. Various reports are available on this topic but results are controversial. During antiangiogenic therapies some authors describe pronounced changes in blood volume: others find effects only on vessel permeability or perfusion. These conflictive observations can be attributed to the different tumor models, therapies, measurement techniques and contrast agents (CA). Particularly the choice of the optimal CA is considered to be essential for a successful characterization of tumor angiogenesis. Often therapy effects on vessel permeability only become apparent, when blood pool CA are used. This article reviews the current state of DCE and molecular MRI of angiogenesis. Besides a general introduction of the different measurement and postprocessing methods and its previous applications, design, structure and use of different types of CA are the main focus of this article.