The introduction and diffusion into widespread clinical practice of a workable procedure for thallium-201 cardiac perfusion imaging was based on a number of distinct discoveries and developments. The various components of the procedure currently in use were developed piecemeal by different individuals at different institutions.
One of the important preconditions for the use of thallium-201 as a perfusion imaging agent was the development of a functional gamma camera. Development of the Anger camera by Hal Anger met this need, moving camera technology beyond the plateau it had achieved in 1960s. This linked array of photomultiplier tubes permitted higher-resolution pictures of the areas of the myocardium perfused by the radioactive tracer. This basic design was substantially refined by manufacturers who increased the number of photomultiplier tubes, improved collimators, added tomographic imaging capabilities, and increased the number of scanning heads in an effort to improve resolution.
Some of the most significant early development work on the imaging agent was carried out by Elliot Leibowitz, then a radiochemist at Brookhaven National Laboratories. He described thallium as a potassium analogue and recognized the relationship between blood flow and thallium uptake by the myocardium that is the foundation of thallium's usefulness as a perfusion imaging agent. He also developed a procedure for postirradiation purification of the cyclotron-produced radioisotope that was suitable for use in commercial-scale production.
Another key step in the development of the procedure took place at Massachusetts General Hospital, where time-delayed imaging studies carried out by Jerry Pohost explored the redistribution properties of thallium-201. These studies showed that over a period of hours following the initial injection of the radioisotope, it would redistribute to those portions of the heart that had initially experienced restricted blood flow. Reversible perfusion defects, it was found, served as markers for ischemic but viable areas of the myocardium. This discovery became the foundation for the development of the exercise-rest double-imaging protocol that is still used today.
A number of regulatory factors facilitated the rapid spread of thallium imaging in clinical practice. The toxicology of thallium was well known from prior applications. In 1974, the Atomic Energy Commission announced that it was turning the regulation of radiopharmaceuticals over to the Food and Drug Administration. The actual transfer occurred 18 months later, just as the cardiac imaging procedures for thallium-201 were being refined. Thus, the FDA, because of its lack of experience, was not in a position to make onerous regulatory demands. New England Nuclear (NEN), the company leading the effort to commercialize thallium-201 for radionuclide scanning, also benefited from its location