NEWS

Standard Imaging Techniques May Monitor Angiogenesis

Donna Pillittere

Research has focused on developing technology useful in predicting and monitoring the response of cancerous tissues to antiangiogenesis agents, and the results have been mixed. But a handful of scientists are looking specifically at a small group of effective noninvasive methods that may be used to detect early changes in blood supply within Kaposi’s sarcoma lesions.

Tumor angiogenesis is among the early changes that differentiate normal tissues from cancerous tissues. More than 20 angiogenesis inhibitors are being tested in human trials (see related story, p. 1202).

"Angiogenesis is a critical pathway in the pathogenesis of Kaposi’s sarcoma, of other cancers, and other diseases," Ellen Feigal, M.D., deputy director of the Division of Cancer Treatment and Diagnosis at the National Cancer Institute, said at the Fourth Annual International AIDS Malignancy conference. Feigal chaired a roundtable discussion where several technologies for monitoring antiangiogenesis therapies were presented.



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Dr. Ellen Feigal

 
One way to monitor this development of blood vessels is with an infrared camera. "We sought to develop a method for rapid, noninvasive evaluation of the activity in KS lesions using images of such lesions obtained with a high-sensitivity infrared camera," said Jerry R. Williams, Sc.D., of Johns Hopkins University, Baltimore. The technology sees through the skin to show the vascularity of the lesion. Williams and colleagues observed differences in infrared images in KS lesions in patients whose disease was active or inactive, and interpreted these images as showing elevated temperature in active lesions.

"We hypothesize that these differences reflect differences in blood flow in active lesions that elevates temperature in lesions compared to adjacent uninvolved skin," said Williams. "This technology could be especially useful in monitoring response of individual lesions to therapy, particularly antiangiogenesis therapy," he said. Attempts are under way to optimize hardware and software to provide instruments to clinics for such monitoring.

Ultrasound

"The use of high-frequency ultrasound to measure blood flow velocities and percentage of apoptotic cells make it a unique tool for the assessment and monitoring of angiogenically active processes in tissue," said Kathy Ferrara, Ph.D., University of California at Davis. Because antiangiogenesis therapies may act in vivo by inducing receptor-mediated apoptosis in activated microvascular endothelial cells, apoptosis may act as an early indicator of response, or lack of response, to therapy. She said studies have shown that apoptotic cells have an increased echogenicity—the rise in reflections (echoes) of ultrasound waves.

Ferrara said that this technology should be further developed and evaluated in mouse models to improve and validate its quantitative abilities in regard to the monitoring of angiogenesis.

"In particular, emphasis should be placed on examination of vessel morphology, as this aspect of angiogenesis is not readily studied with other imaging methods," she said. She added that the results of these efforts should then be translated to clinical studies of ocular melanoma, malignant melanoma, basal cell carcinoma, and Kaposi’s sarcoma and their responses to antiangiogenic treatment.

Several other technologies, such as magnetic resonance imaging, are being investigated as tools to measure angiogenesis. However, the experts agreed that none of the techniques have been validated in trials that have specific endpoints.



             
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