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Discovery of [ <sup>18</sup> F]PSMA-7, a novel PET-probe for the detection of small PSMA positive lesions
摘要： Prostate specific membrane antigen (PSMA) expressed by the vast majority of prostate cancers (PCa) is a promising target for PCa imaging. The application of PSMA specific 18F-labeled PET probes like 18F-DCFPyL and 18F-PSMA-1007 considerably improved the accuracy of PCa tumor detection. However, there remains a need for further improvements regarding sensitivity and specificity. The aim of this study was the development of highly selective and specific PSMA probes with enhanced imaging properties, in comparison with 18F-DCFPyL, 18F-PSMA-1007 and 68Ga-PSMA-11. Methods: Eight novel 18F-labeled PSMA ligands were prepared. Their cellular uptake in PSMA+ LNCaP C4-2 and PSMA– PC-3 cells was compared to that of 18F-DCFPyL. The most promising candidates were additionally evaluated by μPET in healthy rats using PSMA+ peripheral ganglia as a model for small PCa lesions. PET images of the ligand with the best outcome, 18F-JK-PSMA-7, were compared to those of 18F-DCFPyL, 18F-PSMA-1007 and 68Ga-PSMA-11 with respect to key image quality parameters for the time frame 60-120 min. Results: Compared to 18F-DCFPyL, 18F-JK-PSMA-7 demonstrated increased PSMA specific cellular uptake. While target-to-background ratios of 18F-DCFPyL and 18F-PSMA-1007 were comparable, this parameter was higher for 18F-JK-PSMA-7 and lower for 68Ga-PSMA-11. Image acutance was significantly higher for 18F-JK-PSMA-7 and 18F-PSMA-1007 compared to 18F-DCFPyL and 68Ga-PSMA-11. Image resolution was similar for all four tracers. 18F-PSMA-1007 demonstrated significantly higher blood protein binding and bone uptake than the other tracers. Conclusion: 18F-JK-PSMA-7 is a promising candidate for high quality visualization of small PSMA-positive lesions. Excellent preclinical imaging properties justify further preclinical and clinical studies of this tracer.
关键词： Prostate carcinoma,PSMA,preclinical model,radiofluorination,positron emission tomography,imaging
更新于2025-09-23 15:21:01
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[IEEE 2019 International Conference on Microwave and Millimeter Wave Technology (ICMMT) - Guangzhou, China (2019.5.19-2019.5.22)] 2019 International Conference on Microwave and Millimeter Wave Technology (ICMMT) - Surface Waveguide Leaky-wave Antenna for Single-Side Beam Scanning
摘要： We present a 16-channel readout integrated circuit (ROIC) with nanosecond-resolution time to digital converter (TDC) for pixelated Cadmium Telluride (CdTe) gamma-ray detectors. The pixel array ROIC is the proof of concept of the pixel array readout ASIC for positron-emission tomography (PET) scanner, positron-emission mammography (PEM) scanner, and Compton gamma camera. The electronics of each individual pixel integrates an analog front-end with switchable gain, an analog to digital converter (ADC), configuration registers, and a 4-state digital controller. For every detected photon, the pixel electronics provides the energy deposited in the detector with 10-bit resolution, and a fast trigger signal for time stamp. The ASIC contains the 16-pixel matrix electronics, a digital controller, five global voltage references, a TDC, a temperature sensor, and a band-gap based current reference. The ASIC has been fabricated with TSMC m mixed-signal CMOS technology and occupies an area of mm. The TDC shows a resolution mm of 95.5 ps, a precision of 600 ps at full width half maximum W. In acquisition (FWHM), and a power consumption of mode, the total power consumption of every pixel is W. An equivalent noise charge (ENC) of at maximum gain and negative polarity conditions has been measured at room temperature.
关键词： gamma-ray detectors,low-power electronics,Analog-digital conversion,semiconductor radiation detectors,application specific integrated circuits,positron emission tomography,energy resolution
更新于2025-09-23 15:19:57
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Modular medical imaging agents based on azidea??alkyne Huisgen cycloadditions: Synthesis and prea??clinical evaluation of 18Fa??labeled PSMAa??tracers for prostate cancer imaging.
摘要： The seminal contribution of Rolf Huisgen to develop the [3+2]-cycloaddition of 1,3-dipolar compounds, its azide-alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide-alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to preclinical in vivo evaluation of fluorine-18– labeled PSMA-targeting ‘F-PSMA-MIC’ radiotracers (t? = 109.7 min). Preclinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [68Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]-cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents.
关键词： prostate specific membrane antigen,positron emission tomography,fluorine-18,azide-alkyne Huisgen cycloaddition,modular imaging agents
更新于2025-09-23 15:19:57
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Implementation and validation of time-of-flight PET image reconstruction module for listmode and sinogram projection data in the STIR library
摘要： In this paper, we describe the implementation of support for Time-of-Flight (TOF) Positron Emission Tomography (PET) for both listmode and sinogram data in the open source Software for Tomographic Image Reconstruction (STIR). We provide validation and performance characterization using simulated data from the open source GATE Monte Carlo toolbox, with TOF configurations spanning from 81.2 to 209.6 ps. The coincidence detector resolution was corrected for the timing resolution deterioration due to the contribution of the crystal length. Comparison between the reconstruction of listmode and sinogram data demonstrated good agreement in both TOF and non-TOF cases in terms of relative absolute error. To reduce the reconstruction time, we assessed the truncation of the TOF kernel along Lines-of-Response (LOR). Rejection of LOR elements beyond four times the TOF standard deviation provides significant acceleration of ≈ 45% without compromising the image quality. Further narrowing of the kernel can provide extra time reduction but with the gradual introduction of error in the reconstructed images. As expected, TOF reconstruction performs better than non-TOF in terms of both Contrast-Recovery-Coefficient (CRC) and Signal-to-Noise ratio (SNR). CRC achieves convergence faster with TOF, at lower noise levels. SNR with TOF was superior for early iterations, but with quick deterioration. Higher timing resolution further improved reconstruction performance, while TOF bin mashing was shown to have only a small impact on reconstructed images.
关键词： Medical Imaging,Open-Source Software,Positron Emission Tomography,Monte Carlo,Computer Simulations,Time-of-Flight
更新于2025-09-23 15:19:57
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Diagnostic performance of fluorine-18 fluorodeoxyglucose positron emission tomography in the management of solitary pulmonary nodule: a meta-analysis
摘要： Background: In the setting of solitary pulmonary nodules (SPNs), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is considered a useful non-invasive diagnostic tool though false positive (FP) and false negative (FN) results affects accuracy due to different conditions, such as inflammatory diseases or low-uptake neoplasms. Aim of this study is to evaluate overall diagnostic performance of 18F-FDG-PET/CT for malignant pulmonary nodules. Methods: A computerized research, including published articles from 2012 and 2017, was carried out. 18F-FDG-PET/CT overall sensitivity (Se), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), diagnostic index and odds ratio were pooled. No selection-bias were found according to asymmetry test. Results: A total of twelve studies were included in the meta-analysis. The pooled Se, Spe, PLR, NLR, PPV, NPV and accuracy index (AI) with relative 95% confidence intervals (CI) were 0.819 (95% CI: 0.794–0.843), 0.624 (95% CI: 0.582–0.665), 2.190 (95% CI: 1.950–2.440), 0.290 (95% CI: 0.250–0.330), 0.802 (95% CI: 0.783–0.819), 0.652 (95% CI: 0.618–0.684) and 0.649 (95% CI: 0.625–0.673), respectively. The diagnostic odds ratio (DOR) was 7.049 with a relative 95% CI between 5.550 and 8.944. Conclusions: The results suggest 18F-FDG-PET/CT has good diagnostic accuracy in SPNs evaluation; but, it should not be considered as a discriminatory test rather than a method to be included in a clinical and diagnostic pathway.
关键词： Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT),solitary pulmonary nodules (SPNs),lung cancer
更新于2025-09-19 17:15:36
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First prototyping of a dedicated PET system with the hemisphere detector arrangement
摘要： A strong demand is expected for high-sensitivity, high-resolution, and low-cost brain positron emission tomography (PET) imaging for early diagnosis of dementia as well as for general neuroscience studies. Therefore, we have proposed novel geometries of a hemisphere detector arrangement for high-sensitivity brain imaging, in which an add-on detector at the chin position or neck position helps in sensitivity uniformity improvement. In this study, we developed the first prototype system for proof-of-concept using 4-layer depth-of-interaction detectors, each of which consisted of 16×16×4 Zr-doped GSO crystals with dimensions of 2.8×2.8×7.5 mm3 and a high-sensitivity 64-channel flat-panel photomultiplier tube. We used 47 detectors to form a hemisphere detector with a hemisphere shape of 25 cm inner diameter and 50 cm outer diameter, and we used seven detectors for each of the add-on detectors. The hemisphere detector was realized by multiple rings having different numbers of detectors and a cross-shaped top detector unit covering the top. Performance evaluation showed uniform spatial resolutions of 3-4 mm by the filtered back-projection method. Peak sensitivity was measured as more than 10% at a region near the top of the head, which was achieved with the help of the top detector unit. In addition, using the prototype system, we performed the first FDG clinical test with a healthy volunteer. The results showed that the proposed geometries had high potential for realizing high-sensitivity, high-resolution, and low-cost brain PET imaging. As for the add-on detector position, it was shown that the neck position resulted in higher sensitivity and wider field of view (FOV) than the chin position because the add-on detector at the neck position can be placed continuously to the hemisphere detector and close to the FOV.
关键词： brain imaging,helmet-type PET,dementia,positron emission tomography,brain PET,depth-of-interaction
更新于2025-09-19 17:15:36
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Progress of Coordination and Utilization of Zirconium-89 for Positron Emission Tomography (PET) Studies
摘要： Radiometals have been commonly used in medical applications, and utilization of such metals continues to be an attractive research area. In particular, a variety of radiometals have been developed and implemented for molecular imaging. For such applications, 89Zr has been one of the most interesting radiometals currently used for tumor targeting. Several chemical ligands were developed as 89Zr chelators, and new coordinating methods have also been developed more recently. In addition, immuno-positron emission tomography (PET) studies using 89Zr-labeled monoclonal antibodies have been performed by several scientists. In this review, recent advances to the coordination of 89Zr and the utilization of 89Zr in PET studies are described.
关键词： 89Zr,Ligand,Positron emission tomography (PET),Coordination
更新于2025-09-19 17:15:36
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Silicon photomultipliers with area up to 9 mm2 in a 0.35 μm CMOS process
摘要： Silicon photomultipliers produced using standard complementary metal oxide semiconductor (CMOS) processes are at the basis of modern applications of sensors for weak photon fluxes. They allow in fact to integrate transistor-based electronic components within sensors and provide intelligent read-out strategies. In this paper we investigate the scalability of a 0.35 μm CMOS process to large area devices. We report the design and characterization of SiPMs with a total area of 1 mm2, 4 mm2 and 9 mm2. Cross talk, photon detection efficiency at 420 nm, gain at 2.5 V overvoltage and breakdown voltage temperature coefficient do not depend on the total area of the sensor and are 10%, 35%, 2.5 × 106 and 35 mV/K respectively. The dark count rate scales with the total area of the device as 180 kHz/mm2. The total output capacitance, the decay time of the single photon signal and the single photon time resolution depend on the area of the device. We obtain a capacitance of 66.9 pF, 270.2 pF and 554.0 pF, a decay time of (27.1 ± 0.1) ns, (50.8 ± 0.1) ns and (78.2 ± 0.1) ns and a single photon time resolution of (77.97 ± 0.51) ps, (201.67 ± 0.98) ps and (282.28 ± 0.86) ps for the 1 mm2, 4 mm2 and 9 mm2 SiPMs respectively.
关键词： CMOS,Silicon photomultiplier (SiPM),avalanche breakdown structures,Sensors for Brain Positron Emission Tomography
更新于2025-09-19 17:15:36
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Identification, Characterization, and Optimization of Integrin αvβ6-Targeting Peptides from a One-Bead One-Compound (OBOC) Library: Towards the Development of Positron Emission Tomography (PET) Imaging Agents
摘要： The current translation of peptides identified through the one-bead one-compound (OBOC) technology into positron emission tomography (PET) imaging agents is a slow process, with a major delay between ligand identification and subsequent lead optimization. This work aims to streamline the development process of 18F-peptide based PET imaging agents to target the integrin αvβ6. By directly identify αvβ6–targeting peptides from a 9-mer 4-fluorobenzoyl peptide library using the on-bead two-color (OBTC) cell-screening assay, a total of 185 peptide beads were identified and 5 beads sequenced for further evaluation. The lead peptide 1 (VGDLTYLKK(FB), IC50 = 0.45 ± 0.06 μM, 25% stable in serum at 1 h) was further modified at the N-, C-, and bi-termini. C-terminal PEGylation increased the metabolic stability (>95% stable), but decreased binding affinity (IC50 = 3.7 ± 1 μM) was noted. C-terminal extension (1i, VGDLTYLKK(FB)KVART) significantly increased binding affinity for integrin αvβ6 (IC50 = 0.021 ± 0.002 μM), binding selectivity for αvβ6-expressing cells (3.1 ± 0.8:1), and the serum stability (>99% stable). Our results demonstrate the challenges in optimizing OBOC-derived peptides, indicate both termini of 1 are sensitive to modifications, and show that further modification of 1 is necessary to demonstrate utility as an 18F-peptide imaging agent.
关键词： Fluorine-18,integrin αvβ6,affinity,one-bead one-compound (OBOC),library screening,solid-phase radiolabeling,positron emission tomography (PET),selectivity
更新于2025-09-19 17:15:36
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Reconstruction of PET Images Using Cross-Entropy and Field of Experts
摘要： The reconstruction of positron emission tomography data is a difficult task, particularly at low count rates because Poisson noise has a significant influence on the statistical uncertainty of positron emission tomography (PET) measurements. Prior information is frequently used to improve image quality. In this paper, we propose the use of a field of experts to model a priori structure and capture anatomical spatial dependencies of the PET images to address the problems of noise and low count data, which make the reconstruction of the image difficult. We reconstruct PET images by using a modified MXE algorithm, which minimizes a objective function with the cross-entropy as a fidelity term, while the field of expert model is incorporated as a regularizing term. Comparisons with the expectation maximization algorithm and a iterative method with a prior penalizing relative differences showed that the proposed method can lead to accurate estimation of the image, especially with acquisitions at low count rate.
关键词： field of experts,reconstruction,positron emission tomography
更新于2025-09-19 17:15:36