Medical School Team Discovers Compounds Which Can Illuminate Tumors, Detect Cancer in Laboratory Mice

Using a new tumor-seeking compound injected into the bloodstream, four Harvard Medical School (HMS) professors have developed a system to detect the location and stages of cancerous growths.

HMS Associate Professor of Radiology Ralph Weissleder and three colleagues published a report of their work in the April issue of the journal Nature Biotechnology.

The scientists developed a compound which is injected into the body and produces a fluorescent light when it interacts with enzymes associated with tumors.

When the compound was injected into mice, the scientists could see the light given off around tumors using a tabletop machine which they built for the purpose.

"What a molecular biologist does in a test tube, we try to do in whole living people," said Weissleder.

The scientists' probe, known as a contrast agent, targets a specific enzyme in the tumor known as cathepsin b. The enzyme turns on the compound "like a switch," said Research Fellow in Radiology Ching H. Tung, who co-authored the experiment with first author Weissleder, senior author and Assistant Professor of Radiology Alexei A. Bogdanov and Clinical Fellow in Radiology Umar Mahmood.

The experiment marks the first time that anybody has imaged enzyme activities on living creatures, said Weissleder, and this sets the stage for taking their new knowledge into clinics for use on humans.

The findings have applications beyond tumor detection in mice. Tung said that the knowledge could potentially be used for tumor characterization, to classify the tumors and determine the tumors' stages, since tumors behave differently at the different stages of their development.

The findings could potentially be used to evaluate an anti-cancer drug designed to suppress enzymes inside tumors. If the enzymes are suppressed, they will not turn on the probe signal. Scientists would consider the lowered response to the probe a good sign.

"For regular tumor detection right now there is a lot of misdiagnosis because you can't diagnose the early stage of the tumor growth," said Tung. "We've developed contrast agents so hopefully we can detect the signal from the tumor, and detect the tumor, earlier."

"It can be used to look for tumors, but it has much broader ramifications," said Weissleder.

He said that the broader applications include looking for enzyme activities in other diseases, including autoimmune diseases and infections.

The scientists began experimenting about two years ago. They conducted their research at Massachusetts General Hospital in Boston, one of HMS' teaching hospitals.