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

Abstract

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 124 I and a mix of 124 I and 18 F in phantoms and mice. In addition to positrons (mean range 3.4 mm) 124 I emits large amounts of 603 keV prompt gammas that-aided by excellent energy discrimination of NaI-were selected to reconstruct 124 I images that are unaffected by positron range. Photons detected in the 511 keV window were used to reconstruct 18 F images. Images were reconstructed iteratively using an energy dependent matrix for each isotope. Correction of 18 F images for contamination with 124 I annihilation photons was performed by Monte Carlo based range modelling and scaling of the 124 I prompt gamma image before subtracting it from the 18 F image. Additionally, prompt gamma imaging was tested for 89 Zr that emits very high-energy prompts (909 keV). In Derenzo resolution phantoms 0.75 mm rods were clearly discernable for 124 I, 89 Zr and for simultaneously acquired 124 I and 18 F imaging. Image quantification in phantoms with reservoirs filled with both 124 I and 18 F showed excellent separation of isotopes and high quantitative accuracy. Mouse imaging showed uptake of 124 I in tiny thyroid parts and simultaneously injected 18 F-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.

Advancing 89Zr-immuno-PET in neuroscience with a bispecific anti-amyloid-beta monoclonal antibody - The choice of chelator is essential

“…The use of this bispecific mAb, consisting of an amyloid-beta targeting aducanumab derivate and the BBB shuttling moiety 8D3, for immuno-PET imaging, has previously been established by Syvänen et al using iodine-124 as the PET radionuclide [9][10][11]. Despite having an ideal half-life for immuno-PET, iodine-124 suffers from limited availability, high costs, and high positron energy which limits high resolution imaging [21,22]. Therefore, the second aim was to compare the residualizing radiometal zirconium-89 to the non-residualizing iodine-125 (as a substitute for iodine-124) by comparison of the biodistribution of the respective radiolabeled Adu-8D3.…”

Hybrid PET/Compton-camera imaging: an imager for the next generation

“…In vivo 2D and 3D images were obtained injecting three radiotracers simultaneously to a mouse under anesthesia [56]. Si/CdTe Compton cameras have also been employed for multi-isotope imaging of small animals [57,58] and even a human volunteer who was injected intravenously 30 MBq of 99m Tc-DMSA and 150 MBq of 18 F-FDG simultaneously [59]. Such systems demonstrated in vivo multi-isotope imaging with a Compton camera, while the performance was still far from PET and SPECT and the systems were not suitable for being operated in a clinical environment.…”

“…The system was tested both in PET and Compton modes independently with different sources, and also in both modalities simultaneously rotating the PET system to acquire tomographic images. Two 10-ml syringes filled with 18 F-FDG and with 111 InCl 3 were placed at the center. Images were reconstructed employing MLEM and FBP for PET and Compton respectively.…”

“…Although most conventional PET radionuclides are pure positron emitters, such as 18 F, radionuclides with further decay modes have also become relevant in nuclear medicine, broadening the spectrum of PET applications but also posing new challenges to the instrumentation [32]. In particular, some of those radionuclides emit additional gamma-rays in the decay process, either in cascade with the positron as for 124 I, or after some delay, as a result of electron capture (e.g., 89 Zr).…”

“…The spatial resolution of PET images is intrinsically limited by the range of the positron, which depends on the radionuclide. Whereas the resolution degradation is negligible for 18 F, the most used PET radionuclide, it becomes a relevant source of image degradation in the case of 15 O, 68 Ga or 82 Rb, to cite a few. In the last years, new developments in radionuclide targeted therapy offer new ground for PET and SPECT as imaging tools in theranostics (or theragnostics).…”