A research team has demonstrated a new PET imaging approach capable of visualizing three radiotracers at once, marking a step forward in multiplexed imaging.

The findings, presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2025 Annual Meeting, highlight the potential for capturing a more detailed molecular snapshot of disease processes in a single scan.

Triplexed PET, as the technique is called, combines a pure positron emitter with two prompt-gamma plus positron emitters in one imaging session. The study used fluorine-18 (simulated), copper-64, iodine-124, and cobalt-55 to evaluate performance across both simulations and physical experiments.
“The concept of multiplexed PET was reported more than a decade ago, but only within the past five years have the needed radionuclides, radiochemistry, and clinical applications come together to make the approach very interesting,” said Sarah Zou, a PhD candidate in electrical engineering at Stanford University. “With the right tools now in place, our study utilized triplexed PET to image three isotopes in one session.”

To separate the radiotracer signals, researchers sorted photon coincidence data by both photon count and energy. This produced three listmode datasets that were further processed to eliminate isotope crosstalk using scaling factors, allowing for reconstruction of distinct images for each isotope. The team reported successful unmixing of the radiotracers in both simulation and experimental measurements using a phantom with overlapping isotope mixtures.

“This study demonstrates using both simulations and experiments strong potential for performing multiplexed PET with three—or even more—distinct isotopes,” said Zou. “It offers a powerful tool for imaging biologically complex diseases like cancer that involve multiple biomarkers.”

Future efforts will aim at refining quantitative analysis and improving correction techniques. Zou noted that collaboration with industry on scanner hardware and software could make triplexed PET clinically feasible within five years.

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