Compound Developed at MIT Provides Images of Brain's Dopamine Transporters


CAMBRIDGE, MA -- A new brain-imaging agent developed by MIT Professor of Chemistry Alan Davison and colleagues may lead to earlier and more accurate diagnosis of Parkinson's disease and other conditions such as deprression in older people and attention deficit disorder (ADD).

The compound called technepine binds to dopamine transporters in the brain's striatum. The dopamine transporter carries the brain chemical to receptors; it is a marker for several disorders and is also affected by use of drugs including cocaine and alcohol.

Technepine is a compound based on technetium, an element that is "the workhorse of diagnostic nuclear medicine," Professor Davison said. When it is introduced into an affected portion of a patient's body as a short-lived radioactive "tag," it allows scientists and physicians to obtain detailed images of the functioning of that region. A different technetium compound was the basis for Cardiolite, patented in 1984 by Professor Davison, Michael J. Abrams and Alun G. Jones (colleagues at Harvard) that is now widely used for heart perfusion imaging. It is also showing promise in the detection of breast tumors that cannot be identified by conventional mammography, in a technique called scintimammograpy. In fact, Cardiolite is one of the most financially successful inventions by an MIT researcher, according to the Technology Licensing Office.

The technepine research was reported in the March issue of Synapse by Dr. Bertha K. Madras of Harvard Medical School's New England Regional Primate Center; Professor Davison; Alun G. Jones, professor of radiology at Harvard Medical School (Professor Davison's collaborator on Cardiolite); Peter C. Meltzer of Organix, Inc. in Woburn, and others.

Crucial to the success of the work was creating a substance that could reach and concentrate in the brain area of interest. "The technetium-labeled analogue is the first reported compound to cross the blood-brain barrier and accumulate in a selective target, the striatum," the authors reported in the Synapse paper.

In tests on monkeys overseen by Dr. Madras, the animals were placed under general anesthesia, injected with technepine and then subjected to SPECT imaging (single-photon-emission computerized tomography), which revealed the concentration and movement of dopamine transporters. Using a computer program called Superpose developed partly by J. Alex Becker, an MIT graduate student in physics, that image can then be superimposed on an MRI (magnetic-resonance image), resulting in pictures showing both structure and function at various layers of the brain.

Technepine has the added advantage that it can be routinely made in the laboratory and eventually in any hospital radiopharmacy, whereas probes based on radioactive carbon or fluorine must be produced in a cyclotron, Professor Davison said.

If technepine can be successfully used with human patients, it would be an important tool for diagnosing ailments and monitoring treatment efficacy. Some medicines that alter the levels of dopamine and other brain chemicals already exist, "but psychiatrists have only the subjective report of how it's working--they can't see it on a molecular level," Professor Davison said. "This can give us a clue to early diagnosis of Parkinson's disease, for example; it might help us design more effective drugs because you can see what's happening."

MIT and Harvard have applied jointly for a patent on technepine. Professor Davison's research was supported by the National Institutes of Health.


Topics: Chemistry and chemical engineering, Health sciences and technology, Biology

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