Evolution from empirical dynamic contrast-enhanced magnetic resonance imaging to pharmacokinetic MRI

For chemotherapy to be effective against cancers which grow as solid tumors, agents must reach all tumor cells in effective quantities. Although many clinical trials include studies of the pharmacokinetics of the agents in body fluids such as blood or cerebrospinal fluid (CSF), there is presently no widely applicable way to determine access of chemotherapeutic agents to all regions of a solid tumor in an individual patient. This review discusses a relatively new methodology in MR imaging — dynamic contrast-enhanced imaging for exploring tumor microcirculation and drug access by imaging the uptake, or leakage, of contrast agent into tumor interstitial (extracellular and extravascular) space. The aims and methods of dynamic contrast-enhanced MRI evaluations to measure contrast uptake are distinguished from dynamic contrast-enhanced MRI to measure blood volume or flow, by MR imaging of the first-pass effects of a contrast bolus. Measures of contrast uptake by dynamic MRI have demonstrated a convincing ability to aid in diagnosing the presence of viable tumor and to measure response for a range of human tumors. This body of clinical results will be summarized. While questions remain to be answered about how to extract non-invasive pharmacokinetic measures of drug access from these novel dynamic imaging methods, we are optimistic that these methods can provide important new clinical measures that reflect the range of biological variation within and between naturally-occurring solid tumors.