Report from SMI: SPECT test of apoptosis identifies vulnerable carotid artery plaques

One of the first human studies of technetium-labeled Annexin 5A (AA5) has found that the agent can distinguish between stable and unstable carotid plaques, potentially helping vascular surgeons select patients for carotid artery endarterectomy.

Dr. Leonard Hofstra, an associate professor of cardiology, and colleagues in the cardiovascular research institute at Maastricht University Hospital in the Netherlands studied 16 patients with confirmed severe carotid artery stenosis to determine if the agent's known ability to identify regions of high apoptotic activity could noninvasively identify unstable plaques.

Patients were examined with Tc-99m AA5 SPECT before undergoing previously scheduled carotid endarterectomy. The degree of carotid stenosis was 70% to 90%, according to coauthor Sander Wolters. Findings were presented at the 2005 Society for Molecular Imaging meeting in Cologne, Germany.

Morphologic features confirmed that unstable plaques in four patients had positive AA5 scans, according to Wolters. Histologic characteristics included large necrotic cores, macrophagic infiltration, and the presence of AA5, a biomarker of apoptosis.

Nine of 10 cases where no AA5 uptake was observed correlated with histologically confirmed stable atherosclerotic disease. Patient population size was not large enough to statistically calculate the test's accuracy, Wolters said.

The findings build on initial results based on four patients reported in The New England Journal of Medicine.

Although the AA5 scientific research is the cutting edge of molecular imaging, the clinical problem it seeks to address has dogged physicians and healthcare policymakers since the 1980s. The appropriateness of carotid endarterectomy was addressed in a landmark healthcare utilization study from Dartmouth University that found wide variation in the U.S. The more recent European Carotid Surgery Trial and North American Carotid Surgery Trail found that 70% of the expensive and potentially risky elective surgeries are unnecessary, Wolters said. About 500,000 endarerectomies are performed annually in the U.S.

The Maatricht group is laying the groundwork for a multicenter trial of 100 to 200 subjects to determine definitively if plaque stability, measured with Tc-99m AA5 SPECT, can address this problem.

"We want to provide clinicians with a new diagnostic protocol that tells them if a plaque is unstable or stable instead of large or small," he said.