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 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.

Highlights

  • Preclinical PET and SPECT scanners are important devices for basic and translational research

  • All images were reconstructed using 50 iterations DM-SR-OSEM and Gaussian post-filtered with a FWHM of 0.5 mm, 0.5 mm, 0.55 mm, 0.60 mm and 0.65 mm respectively to get proper visualization at the increasing noise level with lower activity

  • All images were reconstructed using 100 iterations DM-SR-OSEM and Gaussian post-filtered with a FWHM of 0.5 mm, 0.5 mm, 0.6 mm and.0.8 mm respectively to get proper visualization at the increasing noise level with lower activity

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Summary

Introduction

Preclinical PET and SPECT scanners are important devices for basic and translational research. The mouse is the most commonly used experimental animal due to its high similarity with the human homolog, today’s existence of many mature genetic manipulation techniques, ease of fast breading and availability of economical housing. Clinical scanners have resolutions ranging from 3 to 6 mm for PET and 8–10 mm for SPECT. As most mouse organs are roughly an order of magnitude smaller than their human counterparts, sub-mm resolution is required to measure molecule concentrations in similar sub-structures in organs and tumors. Like clinical PET, preclinical PET is commonly based on coincidence detection of photons resulting from annihilation of an emitted positron with an electron in neighboring tissue. Resolutions down to 0.8 mm have been reported in high-end commercial coincidence PET systems (Yang et al 2004, Miyaoka et al 2004, Rouze et al 2004, Tai et al 2005) but only for isotopes with very small positron ranges

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