SPECT for Venous Thrombi, Lung Emboli in Human Trials

By Doug Brunk

SAN DIEGO -- The most effective way to detect venous thrombi and pulmonary emboli may involve combining radiolabeled anti-D-dimer antibody fragments with single-photon emission computed tomography, Timothy A. Morris, M.D., said at the 100th International Conference of the American Thoracic Society.

The technique has been performed in dogs but is now being studied for detecting deep venous thrombosis (DVT) in humans, said Dr. Morris of the division of pulmonary and critical care medicine at the University of California, San Diego.

Another trial using the technique to diagnose pulmonary emboli (PE) in humans is expected to begin later this year.

"Despite the advancements in refining clinical probability and serologic tests for thrombosis and advancements in screening, every time anybody tries to see what kind of patients are dying from PE, you get the same answer," Dr. Morris commented. "The people who die from PE are the ones that we never find the PE on in the first place and in fact never suspected."

At Dr. Morris' institution, "the percent of autopsies in which PE is the culprit has not changed very much over the last 35 years," he said. "In addition, the proportion of those patients who die from PE in whom the disease was not suspected premortem does not seem to be changing very much."

Current techniques used to detect venous thrombi, including angiography, ventilation/perfusion scanning, and contrast-enhanced computed tomography "are really detecting both DVT and PE as filling defects," he said. "The actual structure of the clot is irrelevant to the test. There are also some adverse effects [from testing], and no one test is applicable to all of the areas where a clot could occur and all the ages that a clot could be."

Dr. Morris said that the idea of specifically targeting blood clots has been tried before. However, attempts in the late 1980s and early 1990s to use a fibrin-specific contrast agent with nuclear medicine scanning were disappointing. The scans required about 24 hours to image deep vein thrombi, and couldn't image pulmonary emboli.

This was because previous investigators targeted the wrong epitope on fibrin.

Over the past 8 years, Dr. Morris and his associates have devised a different strategy that targets the D-dimer region of fibrin (Am. J. Respir. Crit. Care Med. 2004;169:987-93).

"If we could use an antibody to the D-dimer, every area on the fibrinogen polymer that has a D-dimer is going to be a target for binding," even if a patient is on anticoagulants, he said. "Then we can do functional imaging, so we can say that these clots are going to light up on SPECT scans based on the fact that they are thrombi."

On SPECT scans, the clots resemble "light bulbs" or "hot spots," making them readable in a large blood pool background. The technique can detect a DVT as small as 0.5 grams in size and a PE as small as 0.4 grams.

"It detects only defects that represent clots," he said. "So if there are vascular scars from an old DVT, it's not going to stick to it. It has a very nice biological rationale that [tells you] 'whatever you're not seeing is not a clot.' Then you have no reason to give an anticoagulant [in that case]. If there is no fibrin on it, then there's no reason why an anticoagulant would be helpful."

He added that the SPECT scans need not be read by highly specialized radiologists for confirmation. "This new technique is not dependent on that at all," he said. "What we're looking for is light bulbs."

Dr. Morris estimated that in clinical practice, the technique would not cost more than current imaging techniques used to detect venous thrombi.