Mini EXPLORER II: a prototype high-sensitivity PET/CT scanner for companion animal whole body and human brain scanning

Liu, Yang; Lv, Xinyu; Liu, Weiping; Judenhofer, Martin S.; Zwingenberger, Allison L.; Wisner, Erik R.; Berg, Eric; McKenney, Sarah E.; Leung, Edwin; Spencer, Benjamin A.; Cherry, Simon R.; Badawi, Ramsey D.

doi:10.1088/1361-6560/aafc6c

Cited by 40 publications

(29 citation statements)

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“…Each crystal has dimensions of 2.76 · 2.76 · 18.1 mm. The uEXPLORER has time-of-flight (TOF) capability, with a system timing resolution of approximately 430 ps and energy resolution of 11.7% (7). A summary of the physical characteristics of the uEXPLORER is provided in Table 1.…”

Section: Scanner Descriptionmentioning

confidence: 99%

“…To overcome the limitation of low sensitivity and short AFOV in current clinical PET scanners, the EXPLORER Consortium has been developing very large AFOV imaging systems to offer a transformative platform for biomedical research and clinical applications (5). To date, the consortium has built a 45-cm-long photomultiplier tube-based PET system for nonhuman primate imaging (mini-EXPLORER-I) (6), a 48-cm-long silicon photomultiplierbased PET system for veterinary medical imaging (mini-EXPLORER-II) (7), a scalable 70-cm-long digital silicon photomultiplier PET system for torso imaging (PennPET EXPLORER) (8), and a recently completed 194-cm-long PET/CT system for total-body imaging (uEXPLORER is the product name of the 194-cm-long PET/CT device built by United Imaging Healthcare, and we use this name to refer to the specific scanner tested in this work) (9). Compared with conventional scanners, the massively increased sensitivity of the uEXPLORER improves PET image quality through a high signal-to-noise ratio that supports high spatial and temporal resolution and is also predicted to provide much better lesion detection and region-of-interest (ROI) quantification (10,11).…”

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Total-Body Dynamic Reconstruction and Parametric Imaging on the uEXPLORER

et al. 2019

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Total-Body Dynamic Reconstruction and Parametric Imaging on the uEXPLORER

et al. 2019

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“…High-quality images have been obtained for low-dose high-temporal-resolution dynamic imaging (Zhang et al 2017b). A second device (mini-EXPLORER-II) with broadly similar geometry but smaller crystals and better timing resolution has also been developed by United Imaging Healthcare (UIH) (Lv et al 2017).…”

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confidence: 99%

Theoretical study of the benefit of long axial field-of-view PET on region of interest quantification

et al. 2018

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The aim of this study is to evaluate the benefit of long axial field-of-view (AFOV) PET scanners on region of interest (ROI) quantification. We simulated a series of PET scanners with an AFOV ranging from 22 cm to 220 cm. A theoretical framework was used to predict the contrast recovery coefficient (CRC) and the variance of ROI quantification in penalized maximum likelihood (ML) image reconstruction, in which the resolution and noise tradeoff was controlled by a regularization parameter with a quadratic penalty function. The characterization was based on the converged penalized ML reconstruction with an accurate system model. We examined quantification of a 2 mm ROI and 10 mm ROI in a clinically relevant scan range of 110 cm. Multiple bed positions with 50% overlap were used for scanners with shorter AFOV to provide a relatively uniform sensitivity across the 110 cm axial range. A uniform water cylinder of 20 cm in diameter and 230 cm in length was chosen to model the attenuation and background activity. We computed the variance reduction factor at fixed resolution. Effects of different detector capabilities, including TOF (time-of-flight) resolution (320 ps, 500 ps, and non-TOF) and DOI (depth-of-interaction) resolution (4 mm, 10 mm, and no DOI), were evaluated. The results show that at a normal activity level (370 MBq), the 220 cm AFOV scanner offers a ∼17-fold variance reduction for the 2 mm ROI and ∼26-fold variance reduction for the 10 mm ROI (both measured at CRC = 0.5) over the 22 cm AFOV scanner when both using detectors with 500 ps TOF resolution no DOI capability. The variance reduction factors of trues-only are higher than those of including scatters and randoms. Combining 320 ps TOF and 4 mm DOI, the 220 cm long scanner offers a ∼45-fold variance reduction over the 22 cm long reference scanner (500 ps TOF, no DOI) for imaging 2 mm and 10 mm ROIs. The variance reduction factors are higher at a lower activity level due to lower random fraction. In conclusion, our study demonstrates that a long AFOV scanner can greatly improve the quantitative accuracy of PET imaging compared to current state-of-the-art clinical PET scanners.

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“…There have been several recent developments in high-sensitivity PET systems that are suitable for human and nonhuman primate imaging (1)(2)(3)(4). In these scanners, substantial sensitivity gains have been achieved by extending the scanner's axial length up to approximately 2 m for a human imaging system and to approximately 50 cm in preclinical systems.…”

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Total-Body PET and Highly Stable Chelators Together Enable Meaningful ⁸⁹Zr-Antibody PET Studies up to 30 Days After Injection

Berg

Gill²,

Mařı́k³

et al. 2019

J Nucl Med

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See an invited perspective on this article on page 451. The use of 89 Zr-antibody PET imaging to measure antibody biodistribution and tissue pharmacokinetics is well established, but current PET systems lack the sensitivity needed to study 89 Zr-labeled antibodies beyond 2-3 isotope half-lives (7-10 d), after which a poor signal-to-noise ratio is problematic. However, studies across many weeks are desirable to better match antibody circulation half-life in human and nonhuman primates. These studies investigated the technical feasibility of using the primate mini-EXPLORER PET scanner, making use of its high sensitivity and 45-cm axial field of view, for total-body imaging of 89 Zr-labeled antibodies in rhesus monkeys up to 30 d after injection. Methods: A humanized monoclonal IgG antibody against the herpes simplex viral protein glycoprotein D (gD) was radiolabeled with 89 Zr via 1 of 4 chelator-linker combinations (benzyl isothiocyanate-DFO [DFO-Bz-NCS], where DFO is desferrioxamine B; DFO-squaramide; DFO*-Bz-NCS, where DFO* is desferrioxamine*; and DFO*-squaramide). The pharmacokinetics associated with these 4 chelator-linker combinations were compared in 12 healthy young male rhesus monkeys (∼1-2 y old, ∼3 ± 1 kg). Each animal was initially injected intravenously with unlabeled antibody in a peripheral vessel in the right arm (10 mg/kg, providing therapeutic-level antibody concentrations), immediately followed by approximately 40 MBq of one of the 89 Zr-labeled antibodies injected intravenously in a peripheral vessel in the left arm. All animals were imaged 6 times over a period of 30 d, with an initial 60-min dynamic scan on day 0 (day of injection) followed by static scans of 30-45 min on approximately days 3, 7, 14, 21, and 30, with all acquired using a single bed position and images reconstructed using time-offlight list-mode ordered-subsets expectation maximization. Activity concentrations in various organs were extracted from the PET images using manually defined regions of interest. Results: Excellent image quality was obtained, capturing the initial distribution phase in the whole-body scan; later time points showed residual 89 Zr mainly in the liver. Even at 30 d after injection, representing approximately 9 half-lives of 89 Zr and with a total residual activity of only 20-40 kBq in the animal, the image quality was sufficient to readily identify activity in the liver, kidneys, and upper and lower limb joints. Significant differences were noted in late time point liver uptake, bone uptake, and whole-body clearance between chelator-linker types, whereas little variation (±10%) was observed within each type. Conclusion: These studies demonstrate the ability to image 89 Zr-radiolabeled antibodies up to 30 d after injection while maintaining satisfactory image quality, as provided by the primate mini-EXPLORER with high sensitivity and long axial field of view. Quantification demonstrated potentially important differences in the behavior of the 4 chelators. This finding supports further investigation.

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Mini EXPLORER II: a prototype high-sensitivity PET/CT scanner for companion animal whole body and human brain scanning

Cited by 40 publications

References 41 publications

Total-Body Dynamic Reconstruction and Parametric Imaging on the uEXPLORER

Total-Body Dynamic Reconstruction and Parametric Imaging on the uEXPLORER

Theoretical study of the benefit of long axial field-of-view PET on region of interest quantification

Total-Body PET and Highly Stable Chelators Together Enable Meaningful ⁸⁹Zr-Antibody PET Studies up to 30 Days After Injection

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Mini EXPLORER II: a prototype high-sensitivity PET/CT scanner for companion animal whole body and human brain scanning

Cited by 40 publications

References 41 publications

Total-Body Dynamic Reconstruction and Parametric Imaging on the uEXPLORER

Total-Body Dynamic Reconstruction and Parametric Imaging on the uEXPLORER

Theoretical study of the benefit of long axial field-of-view PET on region of interest quantification

Total-Body PET and Highly Stable Chelators Together Enable Meaningful 89Zr-Antibody PET Studies up to 30 Days After Injection

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Product

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Total-Body PET and Highly Stable Chelators Together Enable Meaningful ⁸⁹Zr-Antibody PET Studies up to 30 Days After Injection