September 8, 2008

Volume 86, Number 36

pp. 16-17

Radiosynthesis

The Tracer Race

Bethany Halford

Chemists who want to make radiotracers need to be synthesis speed racers. Each moment they spend in the chemical triathlon of synthesizing, purifying, and formulating these molecules, the precious radiolabel is decaying, steadily dimming its usefulness as a beacon in positron emission tomography (PET).

In terms of time, a radiochemist has no more than two to three half-lives of the radionuclide to prepare a tracer for injection. That gives chemists working with fluorine-18—which has a half-life of 110 minutes—just a few hours to assemble their PET agents. But that's a leisurely pace compared with carbon-11-labeled compounds, which fizzle out much faster, thanks to the nuclide's 20-minute half-life.

"When you make a radiotracer, you can't reflux your reaction overnight and work it up the next morning," says Chester A. Mathis, a professor of radiology and director of the PET facility at the University of Pittsburgh. "If you did that, there'd be nothing left in the morning in terms of radioactivity."

With time being such a critical element, the radioactive nuclide has to be installed in the final steps of a radiotracer's synthesis. With ¹⁸F, there's enough time for three synthetic transformations once the radiotracer arrives from the cyclotron, where it's made by bombarding stable isotopes with protons and deuterons.

If you're working with ¹¹C, there's usually only time for two steps. "In ¹¹C chemistry we may be performing multistep radiotracer synthesis within an hour," notes Victor W. Pike, chief of PET radiopharmaceutical sciences in the Molecular Imaging Branch of the National Institute of Mental Health.

Chemists who make radiotracers tagged with ¹¹C need to work where there's a cyclotron on-site, but ¹⁸F's longer half-life means the radionuclide can be shipped short distances. Steven M. Larson, chief of nuclear medicine at Memorial Sloan-Kettering Cancer Center, recalls how when he was chief of nuclear medicine at the National Institutes of Health in the 1980s, the closest cyclotron to his lab in Bethesda, Md., was 12 miles away at the Naval Research Laboratory. It wasn't uncommon back then, he says, for traffic around the District of Columbia Beltway to sabotage his tracer synthesis.

These days the distribution of ¹⁸F radiotracers is much more reliable, Larson says. Still, Mathis points out, "most organic chemists would feel an extreme amount of stress" when faced with the challenge of making a radiotracer.

And it's not just the time crunch that radiochemists have to contend with. Because they're working with radioactive materials, all the synthetic machinations and purifications are done by robotic manipulation inside a box with lead-lined walls—all to get less than a microgram of radiotracer. "It's totally different thinking when you put it behind lead glass, and you can't put your hands in," Mathis says.

Chemical & Engineering News

ISSN 0009-2347

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