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Alan Davison, 69, has made numerous contributions to synthetic inorganic chemistry and studies of transition-metal compounds over his long career at Massachusetts Institute of Technology. "But these discoveries, which would be defining to the careers of most, serve only as a backdrop to the contribution for which he is being honored," namely, the invention of the technetium compound Cardiolite, a cardiac imaging agent, notes his MIT colleague Daniel G. Nocera. Cardiolite "has revolutionized the way in which physicians can image the heart, thereby allowing them to save countless lives by the early diagnosis of heart disease," Nocera explains.
Cardiolite produced $1.5 billion in net sales last year and is the leading cardiac imaging agent in the world. It's the only FDA-approved imaging agent for the noninvasive evaluation of the heart's ability to pump blood and the measurement of the amount of blood flowing to the heart muscle itself. "It allows doctors to ascertain easily which cardiac patients require surgery and which require less invasive medical treatment," explains chemist Chris Orvig of the University of British Columbia.
When technetium coordination chemistry caught Davison's attention in the mid-1970s, the γ-ray emitting 99mTc was widely used in diagnostic nuclear medicine imaging. "But the agents used had been discovered by trial and error," Davison says. Hoping to learn how new technetium radiopharmaceuticals might be designed rationally, his group began to systematically study the basic coordination chemistry of 99Tc.
He and graduate student Michael J. Abrams characterized a series of simple octahedral technetium(III) salts that proved to be a versatile synthetic intermediate. The salts led them to an inert and kinetically stable hexakis(tert-butylisonitrile) technetium complex, which the scientists showed could be readily prepared from the pertechnetate anion, [TcO4-], the starting material typically used for generating technetium radiopharmaceuticals.
Davison and Abrams used this route to synthesize a 99mTc version of the hexakis(tert-butylisonitrile) technetium complex and, with the help of Alun G. Jones at Harvard Medical School, showed that the complex could be used to image the heart in animals. Davison himself was the second human volunteer in the first human studies of the utility of this and related technetium analogs to be used as imaging agents.
Of these analogs, the one with the best heart-to-liver labeling ratio and clearance properties was hexakis(carbomethoxy-2-propylisonitrile)Tc(I), which was licensed to New England Nuclear, a company that has since become part of Bristol-Myers Squibb. The compound is sold under the name Cardiolite for heart imaging. Recently, Bristol-Myers Squibb has begun to market it for detection of early-stage breast cancer.
"Davison realized that fundamental coordination chemistry would shed light on the chemical characteristics of the element technetium and that these basic chemical characteristics could be translated into the rational design of new radiopharmaceuticals," Orvig notes. In addition, "the fundamental chemistry Davison developed also indirectly led to the development of many other diagnostic agents," he adds. "I consider him one of the fathers of medicinal inorganic chemistry."
Having grown up in Wales, Davison earned his B.Sc. in chemistry at nearby University College of Swansea. He completed his Ph.D. in chemistry at Imperial College of Science & Technology, in London. After a brief stint as a chemistry instructor at Harvard University, in 1964 he joined the chemistry faculty at MIT, where he has been ever since. He became an emeritus professor in 2005. He is a fellow of the Royal Society of London.
The award address will be presented before the Division of Inorganic Chemistry.—Amanda Yarnell