Quantitative Imaging of ⁵⁵CO and ¹⁸F-Labeled Tracers in a Single “Multiplexed” Pet Imaging Session

In this study, we explore the use of Cobalt-55 as a radioisotope for multiplexed PET (mPET) by utilizing its emission of a prompt gamma-ray in cascade with a positron during decay. We leverage the prompt-gamma signal to generate triple coincidences for a Co-55-labeled tracer, allowing us to distinguish it from a tracer labeled with a pure positron emitter F-18, which yields a two photon coincidence. By employing this triple versus double coincidence detection and signal processing methodology, we show the potential to separate and quantify the Co-55 signal from that of F-18. Phantom studies showed strong linear correlation <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(R^{2}=0.99)$</tex> between Co-55 double and triple coincidence counts and total Co-55 activity. Finally, we highlight the capability of this method to quantify overlapping and non-overlapping hot spots within a warm background to within a 3 to 15% error range. Moreover, we demonstrate the feasibility of simultaneously imaging two tracers in vivo during a single PET session using mice.