Quantification of Antiangiogenic and Antivascular Drug Activity by Kinetic Analysis of DCE‐MRI Data

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to quantify the response of tumors to vascular targeting agents. Tumor response is frequently assessed using mathematical models that describe the distribution of contrast agents over time as a function of fundamental characteristics of vascular physiology. Generally, mathematical models of biological systems are abstractions that attempt to retain fundamental physiologic characteristics, thereby allowing for multiple potential modeling approaches and structures. Various DCE-MRI modeling techniques are discussed in this article. Magnetic resonance imaging (MRI) allows visualization of human anatomy in a noninvasive manner 1,2 and can also be used in a contrast-agent-enhanced mode. 3–6 Low-molecularweight gadolinium (Gd) chelate contrast agents (t 1/2 ≈ 90 min) are most commonly used in clinical settings because they are well-characterized, highly polar molecules that distribute only to the extracellular space. 3 They are usually excreted unchanged by the kidneys but are contraindicated in patients with severely reduced kidney function (glomerular filtration rate <30 ml/ min) given the risk (albeit a low one) of nephrogenic systemic fibrosis. 7