(Photography: Medioimages/PhotoDisc, Getty Images )
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In oncology research, medical imaging is used to evaluate anatomical biomarkers such as change in tumor size. To document
and quantitatively measure tumor change due to cytotoxic drug treatment, researchers measure and evaluate tumor size using
computed tomography (CT) or magnetic resonance imaging (MRI) scans and Response Evaluation Criteria in Solid Tumors, known
as RECIST criteria.
Figures 1 and 2.
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Emerging cancer therapies known as vascular-targeted compounds halt the flow of blood to and from the tumor, causing cell
death within the tumor well before it actually begins to shrink. This cannot be measured by RECIST assessment. An emerging
imaging procedure known as dynamic contrast-enhanced (DCE)-MRI is a more appropriate measurement of the effectiveness of vascular-targeted
therapies because it can show metabolic changes such as the rate of blood flow to the tumor.
This article will compare vascular-targeted and cytotoxic cancer treatments, introduce the DCE-MRI procedure, discuss the
image acquisition process, and review some important considerations when planning oncology trials.
Cytotoxic vs. vascular-targetedCytotoxic drugs used for the treatment of cancer (chemotherapy) interrupt the division of rapidly dividing cells, resulting
in the shrinkage and ultimate destruction of cancer tumors. For clinical trials focusing on the effects of cytotoxins, tumor
response is used as a biomarker and is measured at various stages using X-ray, CT, and MRI and evaluated by RECIST assessment.
In contrast to cytotoxins that focus on the tumor itself, vascular-targeted treatments disrupt the tumor's blood supply. A
tumor cannot survive without oxygen, which is delivered along with other critical nutrients by the blood. Disrupting the flow
of blood to the tumor prevents the growth of new cells and inhibits tumor expansion.
The formation of new blood vessels by the tumor, known as angiogenesis, can be inhibited by anti-angiogenic treatments. In
contrast, vascular disrupting agents target existing blood vessels. Restricting the tumor's blood flow must take into account—and
possibly target—both new and established vasculature.
The potential of vascular-targeted cancer therapies is widely recognized by the medical and research communities. A variety
of anti-angiogenics and vascular disrupting compounds are in development or undergoing clinical trials. Tumor size, the preferred
biomarker for clinical trials involving conventional chemotherapy agents, is not appropriate for trials involving vascular-targeted
treatments because shrinkage may not occur until well after blood flow has been halted. Instead, DCE-MRI is used to measure
whether blood flow to the tumor has decreased, indicating the success of treatment.
Use and benefits
Primarily used in Phase I, the DCE-MRI provides physicians with two- or three-dimensional images taken as the patient is being
administered an IV solution of paramagnetic contrast, the same gadolinium-based compound used in regular MRI studies.
Specific image acquisition and contrast injection techniques make possible the measurement of blood flow to the tumor. Prior
to dynamic imaging, an initial image is acquired to establish the tumor's location and provide baseline anatomical data. Dynamic
image acquisition consists of continuous scans made at five- to 10-second intervals over a five to 15 minute time frame.
Gadolinium administered concentrates at the tumor. As it circulates through the tumor vasculature, the contrast's paramagnetic
properties permit blood flow to be visualized. Blood flow can be quantified using a special algorithm. Compared to tumor shrinkage,
this biomarker allows the response of blood vessels to vascular-targeted cancer treatments to be detected and measured very
rapidly using DCE-MRI techniques.
DCE-MRI has many benefits in clinical trials. Besides indicating earlier anatomical response to the treatment, the technique
does not involve ionizing radiation. In addition, it provides high-quality images and can be conducted using fairly common
imaging center equipment, the 1.5 Tesla MRI scanner.
