Tomographic technique powerful research tool

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One of the newest and most powerful of nuclear medicine's research tools is positron emission tomography, or PETT, which gives clinicians and researchers a nondestructive means of probing the biochemical process of the body from the outside.

Not surprisingly, PETT was the subject of a number of talks given at a symposium on the practical appli­cations of nuclear and radiochemis-try, organized by Richard A. Lam-brecht and Nabil M. Morcos of Brookhaven National Laboratory for the Second Chemical Congress of the North American Continent held last month in Las Vegas.

In a PETT experiment, the subject is injected with a radiopharmaceuti­cal labeled by a positron emitter, the most commonly used being carbon-11, nitrogen-13, oxygen-15, and fluo­rine-18. The positrons emitted by these atoms travel only a few milli­meters through the surrounding tis­sue before annihilating into two back-to-back, 0.511-MeV gamma rays. Outside the body, the gamma rays are monitored by an array of so­dium iodide scintillation counters. A few minutes of accumulated data allow a computer to reconstruct the radiopharmaceutical's distribution within the body, much as conven­tional x-ray tomography reconstructs an x-ray cross section of the body.

"Use of the technique presently is growing at an exponential rate," says Brookhaven's Alfred P. Wolf, who was unable to give his invited talk on the subject, but who shared his views with C&EN. Following a hiatus after World War II, he says, interest in positron emitters revived in the late 1950's as accelerators became more readily available to chemists and as rapid synthetic processes were de­veloped for a wide variety of organic compounds. The advantages were clear: Not only could the gamma ra­diation be detected from outside the body, allowing research on live ani­mals and on humans, but radiophar­maceuticals could be made that were physiologically identical to the body's own compounds.

In the past five to seven years, Wolf says, positron emitters have received major new impetus from research in neurophysiology, cardiology, and basic cellular biology. For example, it is already possible to make quanti­tative measurements of regional brain glucose and oxygen metabolism with a resolution of 1 to 2 cm, and it soon may be possible to do quantitative regional cerebral blood flow with the same resolution.

" 'Quantitative' is the name of the game," says Wolf. "It's easy to see cerebral blood flow, but it's hard to know exactly what you're looking at."

Applications of PETT brain scans in clinical practice might include more sophisticated diagnosis of psy­chiatric disorders, stroke, and epi­lepsy, says Wolf. The technique also may prove useful in Huntington's disease, tardive dyskinesia, growth rates in brain tumors, senile demen­tia, and other diseases.

In a like manner, ongoing research should make it possible for PETT to assess functional and metabolic ac­tivity in small regions of the heart. In fact, Wolf believes that in the not too distant future the resolution of PETT will be refined from the current 1 to 1.5 cm down to 0.2 cm.

The small cyclotron plays a central role in PETT research, and indeed in nuclear medicine as a whole, Wolf says. As a result, interest and invest­ment in these machines is rapidly increasing worldwide. On the other hand, the half-life of most of the major positron emitters is measured in minutes, making it imperative that they be synthesized on the spot— especially if they ever are to be used in clinical practice. Thus, accelerator

manufacturers have been making a real effort to provide a product that is cheaper than the older machines, more compact, and more amenable to routine use by nonspecialists.

Because of the expense of a PETT facility—the cyclotron/chemistry laboratory/positron tomograph combination costs a great deal more than a CAT scanner, for example, and the total staff requirement is larger—research is likely to be con­fined to a few major centers for some time to come. In fact, the National Institutes of Health recently has begun funding seven such regional centers at Brookhaven; the University of Pennsylvania; the University of California, Los Angeles; Johns Hop­kins University; the University of Michigan, Ann Arbor; the University of Miami; and Sloan-Kettering In­stitute.

A researcher at one such center, Pennsylvania's Abass Alavi, reported to the symposium on the efforts there under principal investigator Martin Reivich to validate the use of fluo­rine- 18-labeled deoxyglucose as a tracer for regional brain metabo­lism.

Labeled or unlabeled, deoxyglucose is absorbed from the blood by active cells that confuse it with normal glu-

Sept. 22, 1980 C&EN 31

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cose, Alavi explains. The higher the cell's energy needs, the more it ab­sorbs. The difference comes once the deoxyglucose is inside, where it proves resistant to some of the met­abolic enzymes. The upshot is that a phosphorylated form of the deoxy-sugar piles up in the cell, providing a rough measure of the cell's activity.

Thus, Alavi says, by labeling deoxyglucose with fluorine-18 and using PETT to image its distribution in the brain, it has proved possible— without sacrificing the graduate stu­dent volunteers—to find out which parts of the brain are working hardest during any given activity.

Compare this with the traditional method for exploring brain function, autoradiography, which uses com­pounds labeled with carbon-14. Be­cause carbon-14 emits electrons, which have a very short path length in tissue, researchers can map its dis­tribution only by slicing up the brains of their experimental animals, placing the slices on film, and letting the ra­dioactive material take its own pho­tograph.

Clearly, the less-destructive PETT technique is more suitable for human subjects, says Alavi.

As a demonstration of PETT, the left side of a subject's visual field was stimulated with high-contrast black and white patterns of lines, or with abstract color images. PETT-gener-ated cross-sectional images of the brain showed a clear increase of ac­tivity in the right side of the visual cortex. The same happens with tactile stimuli.

To demonstrate the utility of the technique in neuropathology, the Pennsylvania team, in collaboration with Wolf's group at Brookhaven, scanned the brain of an epileptic during a petit mal seizure, a "memory lapse.!' As long as the seizure lasted, says Alavi, the patient showed greatly lowered activity in the cerebellum and heightened activity in the right temporal lobe.

The PETT machine currently in use at Pennsylvania can do seven brain slices in 10 to 20 seconds, says Alavi. In the future, the researchers would like to go to one-second scans to follow dynamic effects in the brain. Also, they would like to get away from fluorine-18. With a half-life of 110 minutes it is the easiest positron emitter to use, he says, but that also means that a patient can't be given very much. On the other hand, the two-minute half-life of oxygen-15 may cause some technical problems, but it means that the subject can take a higher dose more safely. A higher dose means a higher counting rate, more reliable data, and better spatial resolution in the final image. D

32 C&EN Sept. 22, 1980

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