Simultaneous quantitative imaging of two PET radiotracers via the detection of positron–electron annihilation and prompt gamma emissions

Edwin C. Pratt, Alejandro Lopez-Montes, Alessia Volpe, Michael J. Crowley, Lukas M. Carter, Vivek Mittal, Nagavarakishore Pillarsetty, Vladimir Ponomarev, Jose M. Udías, Jan Grimm, Joaquin L. Herraiz

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


In conventional positron emission tomography (PET), only one radiotracer can be imaged at a time, because all PET isotopes produce the same two 511 keV annihilation photons. Here we describe an image reconstruction method for the simultaneous in vivo imaging of two PET tracers and thereby the independent quantification of two molecular signals. This method of multiplexed PET imaging leverages the 350–700 keV range to maximize the capture of 511 keV annihilation photons and prompt γ-ray emission in the same energy window, hence eliminating the need for energy discrimination during reconstruction or for signal separation beforehand. We used multiplexed PET to track, in mice with subcutaneous tumours, the biodistributions of intravenously injected [124I]I-trametinib and 2-deoxy-2-[18F]fluoro-d-glucose, [124I]I-trametinib and its nanoparticle carrier [89Zr]Zr-ferumoxytol, and the prostate-specific membrane antigen (PSMA) and infused PSMA-targeted chimaeric antigen receptor T cells after the systemic administration of [68Ga]Ga-PSMA-11 and [124I]I. Multiplexed PET provides more information depth, gives new uses to prompt γ-ray-emitting isotopes, reduces radiation burden by omitting the need for an additional computed-tomography scan and can be implemented on preclinical and clinical systems without any modifications in hardware or image acquisition software.

Original languageEnglish (US)
Pages (from-to)1028-1039
Number of pages12
JournalNature Biomedical Engineering
Issue number8
StatePublished - Aug 2023


  • Male
  • Animals
  • Mice
  • Electrons
  • Positron-Emission Tomography/methods
  • Iodine Radioisotopes
  • Tomography, X-Ray Computed

ASJC Scopus subject areas

  • Bioengineering
  • Biotechnology
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Computer Science Applications


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