Research Spotlight: Differences in the Breakdown of PET Tracer in Awake and Anesthetized States

Pedro Brugarolas, PhD, an investigator at the Center of Nuclear Medicine and Theranostic Sciences at Massachusetts General Hospital and an assistant professor of Radiology at Harvard Medical School, is the corresponding author of a new study in the Journal of Neurochemistry, Common Anesthetic Used in Preclinical Imaging Inhibits Metabolism of the PET Tracer.

Karla Ramos-Torres, PhD, an instructor in investigation in the Department of Radiology at Mass General and an instructor of Radiology at Harvard Medical School, is first author.

What Question Were You Investigating?

We observed marked differences in the brain radioactive signal after administering [18F]3F4AP, a PET tracer for imaging demyelinated axons in the brain, to monkeys and humans, which was unexpected (3x lower tracer in humans than in monkeys). When we mentioned this to colleagues, they all ascribed it to some vague species differences. We wondered whether anesthesia could be the cause since monkeys are imaged anesthetized and humans awake so we designed a study to test this.

What Methods or Approach Did You Use?

We measured the brain radioactivity in mice that received an injection of 3F4AP anesthetized and awake using a gamma counter. We also analyzed the blood of these mice to test if there were differences in the breakdown of the tracer under awake and anesthetized conditions.

What Did You Find?

Sure enough, we found that awake mice had ~3 times lower tracer concentration in the brain than anesthetized mice. Furthermore, we were able to see that anesthetized mice did not break down the tracer but awake mice did which clearly showed that the anesthesia was inhibiting the breakdown of the tracer resulting in an artificially higher signal in anesthetized animals.

What are the Clinical Implications?

New PET tracers are always tested in animals before testing them in humans. Most people assume that the results in animals are a good approximation to what will be seen in humans. We found that anesthesia can have a major effect on tracer brain uptake and metabolism.

What’s Next?

It will be important to see if this effect is generalizable and it occurs with other tracers. If so, the scientific community should consider testing their tracers in anesthetized and non-anesthetized animals before moving to human studies.

Paper Cited:

Ramos-Torres, K., Sun, Y., Takahashi, K., Zhou, Y. P., & Brugarolas, P. (2024). Common anesthetic used in preclinical PET imaging inhibits metabolism of the PET tracer [¹⁸F]3F4AP. Journal of neurochemistry, 10.1111/jnc.16118. Advance online publication. https://doi.org/10.1111/jnc.16118