Positron range-free and multi-isotope tomography of positron emitters

Despite improvements in small animal PET instruments, many tracers cannot be imaged at sufficiently high resolutions due to positron range, while multi-tracer PET is hampered by the fact that all annihilation photons have equal energies. Here we realize multi-isotope and sub-mm resolution PET of isotopes with several mm positron range by utilizing prompt gamma photons that are commonly neglected. A PET-SPECT-CT scanner (VECTor/CT, MILabs, The Netherlands) equipped with a high-energy cluster-pinhole collimator was used to image ¹²⁴I and a mix of ¹²⁴I and ¹⁸F in phantoms and mice. In addition to positrons (mean range 3.4 mm) ¹²⁴I emits large amounts of 603 keV prompt gammas that-aided by excellent energy discrimination of NaI-were selected to reconstruct ¹²⁴I images that are unaffected by positron range. Photons detected in the 511 keV window were used to reconstruct ¹⁸F images. Images were reconstructed iteratively using an energy dependent matrix for each isotope. Correction of ¹⁸F images for contamination with ¹²⁴I annihilation photons was performed by Monte Carlo based range modelling and scaling of the ¹²⁴I prompt gamma image before subtracting it from the ¹⁸F image. Additionally, prompt gamma imaging was tested for ⁸⁹Zr that emits very high-energy prompts (909 keV). In Derenzo resolution phantoms 0.75 mm rods were clearly discernable for ¹²⁴I, ⁸⁹Zr and for simultaneously acquired ¹²⁴I and ¹⁸F imaging. Image quantification in phantoms with reservoirs filled with both ¹²⁴I and ¹⁸F showed excellent separation of isotopes and high quantitative accuracy. Mouse imaging showed uptake of ¹²⁴I in tiny thyroid parts and simultaneously injected ¹⁸F-NaF in bone structures. The ability to obtain PET images at sub-mm resolution both for isotopes with several mm positron range and for multi-isotope PET adds to many other unique capabilities of VECTor's clustered pinhole imaging, including simultaneous sub-mm PET-SPECT and theranostic high energy SPECT.