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Dopamine imaging agent developed

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 ranging from depression in older people to attention deficit disorder (ADD). The compound, dubbed 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, his former graduate student Michael J. Abrams and Alun G. Jones of 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; Dr. Jones, professor of radiology at Harvard Medical School; 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 physicians have only a subjective report of how it's working-they can't see it on a molecular level," Professor Davison said. "If 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.

EDITOR'S NOTE: This clarification regarding information not originally supplied to MIT Tech Talk was published in the issue of August 28, 1996:
"In an article headlined 'Dopamine imaging agent developed' that appeared in the June 5 issue, the patent application information for technepine and the contributions of Drs. P.C. Meltzer and P. Blundell of Organix Inc., of Woburn were incompletely stated. Seeking a patent for technepine are Organix (40 percent), Harvard University (40 percent) and MIT (20 percent). The unlabelled material was synthesized at Organix using methodology similar but not identical to that developed at MIT. The research by Drs. Meltzer and Blundell was funded by a grant from the National Institute on Neurological Diseases and Stroke to Organix (the principal investigator was Dr. Meltzer).

A version of this article appeared in MIT Tech Talk on June 5, 1996.

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