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Tracing Boron with Fluorescence and PET Imaging of Boronated Porphyrin Nanocomplex for Imaging Guided Boron Neutron Capture Therapy
摘要： Boron neutron capture therapy (BNCT) induces high-energy radiation within cancer cells while avoiding damage to normal cells that without uptake of BNCT drugs, which is holding great promise to provide excellent control over locally invasive malignant tumors. However, lack of quantitative imaging technique to determine local boron concentration has been a great challenge for nuclear physicians to apply accurate neutron irradiation during the treatment, which is a key factor that has limited BNCT’s application in clinics. To meet this challenge, this study describes coating boronated porphyrins with a biocompatible Poly(lactide–co-glycolide)–monomethoxy-poly(polyethylene-glycol) (PLGA-mPEG) micelle for selective tumor accumulation and reduced toxicity comparing with previously reported boronated porphyrin drugs. Fluorescence imaging and PET imaging were performed, unveiling the potential imaging properties of this boronated porphyrin nanocomplex (BPN) to locate tumor region and to determine tissue-localized boron concentration which facilitates treatment planning. By studying the pharmacokinetics of BPN with Cu-64 PET imaging, the treatment plan was adjusted from single bolus injection to multiple times of injections of smaller doses. As expected, high tumor uptake of boron (125.17±13.54 ppm) was achieved with an extraordinarily high tumor to normal tissue ratio: tumor to liver, muscle, fat and blood were 3.24±0.22, 61.46±20.26, 31.55±10.30 and 33.85±5.73, respectively. At last, neutron irradiation with BPN showed almost complete tumor suppression, demonstrating that BPN holds a great potential for being an efficient boron delivery agent for imaging-guided BNCT.
关键词： copper-64,boron neutron capture therapy,theranostics,positron emission tomography,micelle
更新于2025-09-23 15:21:21
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Handbook of Neuro-Oncology Neuroimaging || Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT) Physics
摘要： The purpose of emission tomography is to estimate the distribution of a radiotracer from external measurements of the pattern of photons emerging from the brain. Some of these photons are detected, and certain information about them recorded, by the scanner. These external measurements are termed “projections,” and each measurement in a projection represents, ideally, the sum of radioactivity concentration along a line through the brain. From these measured projection data sets and knowledge of certain aspects of the single-photon emission computed tomography (SPECT) or positron emission tomography (PET) instrument, estimated images of the distribution of radioactivity are mathematically reconstructed. All modern SPECT and PET scanners image the three-dimensional (3D) distribution of radioactivity, either as a stack of two-dimensional (2D) transaxial images or directly as a 3D volume.
关键词： Single-Photon Emission Computed Tomography,Positron Emission Tomography,Image Reconstruction,Radiotracer,SPECT,PET,Radioactivity Distribution,Physics
更新于2025-09-23 15:21:01
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<sup>86/90</sup> Y-Labeled Monoclonal Antibody Targeting Tissue Factor for Pancreatic Cancer Theranostics
摘要： Pancreatic cancer is highly aggressive, with a median survival time of less than 6 months and a 5-year overall survival rate of around 7%. The poor prognosis of PaCa is largely due to its advanced stage at diagnosis and the lack of efficient therapeutic options. Thus, the development of an efficient, multifunctional PaCa theranostic system is urgently needed. Overexpression of tissue factor (TF) has been associated with increased tumor growth, angiogenesis, and metastasis in many malignancies, including pancreatic cancer. Herein, we propose the use of a TF-targeted monoclonal antibody (ALT836) conjugated with the pair 86/90Y as a theranostic agent against pancreatic cancer. For methods, serial PET imaging with 86Y-DTPA-ALT836 was conducted to map the biodistribution the tracer in BXPC-3 tumor-bearing mice. 90Y-DTPA-ALT836 was employed as a therapeutic agent that also allowed tumor burden monitoring through Cherenkov luminescence imaging. The results were that the uptake of 86Y-DTPA-ALT836 in BXPC-3 xenograft tumors was high and increased over time up to 48 h postinjection (p.i.), corroborated through ex vivo biodistribution studies and further confirmed by Cherenkov luminescence Imaging. In therapeutic studies, 90Y-DTPA-ALT836 was found to slow tumor growth relative to the control groups and had significantly smaller (p < 0.05) tumor volumes 1 day p.i. Histological analysis of ex vivo tissues revealed significant damage to the treated tumors. The conclusion is that the use of the 86/90Y theranostic pair allows PET imaging with excellent tumor-to-background contrast and treatment of TF-expressing pancreatic tumors with promising therapeutic outcomes.
关键词： pancreatic cancer,yttrium-86,radioimmunotherapy,tissue factor,yttrium-90,theranostics,positron emission tomography (PET)
更新于2025-09-23 15:21:01
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Synthesis and analysis of 64Cu-labeled GE11-modified polymeric micellar nanoparticles for EGFR-targeted molecular imaging in a colorectal cancer model
摘要： Polymeric micellar nanoparticles represent versatile and biocompatible platforms for targeted drug delivery. However, tracking their biodistribution, stability, and clearance profile in vivo is challenging. The goal of this study was to prepare surface-modified micelles with peptide GE11 for targeting the epidermal growth factor receptor (EGFR). In vitro fluorescence studies demonstrated significantly higher internalization of GE11-micelles into EGFR-expressing HCT116 colon cancer cells versus EGFR-negative SW620 cells. Azo coupling chemistry of tyrosine residues in the peptide backbone with aryl diazonium salts was used to label the micelles with radionuclide 64Cu for positron emission tomography (PET) imaging. In vivo analysis of 64Cu-labeled micelles showed prolonged blood circulation and predominant hepatobiliary clearance. The biodistribution profile of EGFR-targeting GE11-micelles was compared with non-targeting HW12-micelles in HCT116 tumor-bearing mice. PET revealed increasing tumor-to-muscle ratios for both micelles over 48 h. Accumulation of GE11-containing micelles in HCT116 tumors was higher compared to HW12-decorated micelles. Our data suggest that the efficacy of image-guided therapies with micellar nanoparticles could be enhanced by active targeting, as demonstrated with cancer biomarker EGFR.
关键词： polymeric micelles,epidermal growth factor receptor (EGFR),64Cu,GE11 peptide,Colorectal cancer,positron emission tomography (PET)
更新于2025-09-23 15:21:01
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High-selectivity bandpass filter using six pairs of quarter-wavelength coupled lines
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： positron emission tomography,low-power electronics,semiconductor radiation detectors,application specific integrated circuits,gamma-ray detectors,Analog-digital conversion,energy resolution
更新于2025-09-23 15:21:01
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[IEEE 2019 IEEE 46th Photovoltaic Specialists Conference (PVSC) - Chicago, IL, USA (2019.6.16-2019.6.21)] 2019 IEEE 46th Photovoltaic Specialists Conference (PVSC) - Doped Layer Characterization Using Accurate Optical Modelling of Mid-Infrared Spectrometry
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), con?guration 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, ?ve 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： positron emission tomography,low-power electronics,application speci?c integrated circuits,semiconductor radiation detectors,gamma-ray detectors,Analog-digital conversion,energy resolution
更新于2025-09-23 15:21:01
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Quantitative assessment of dynamic <sup>18</sup> F-Fluoromethycholine PET and Dynamic Contrast Enhanced MRI in High Risk Prostate Cancer
摘要： Objectives: To describe dynamic 18F-Fluoromethycholine PET (dPET) and dynamic contrast enhancement MR (DCE MR) parameters in localized high-risk prostate cancer (PCa), and determine whether these differ from normal prostate. Furthermore, to determine whether a correlation exists between dPET and DCE MR parameters. Methods: Forty-one consenting patients who underwent prostate DCE MR and dPET were included in this institutionally approved study. Intraprostatic lesions on MR were assigned a PI-RADS v2 score, and focal lesions on PET were documented. All lesions were correlated with pathology. Quantitative and semiquantitative DCE MR and 2-tissue compartmental model dPET parameters were determined and tumor-to-normal gland ratios (T/N) for these parameters were calculated. Finally, dPET and DCE MR correlation was estimated using Spearman correlation coefficients. Results: There were 46 malignant lesions per standard of reference. On dPET, peripheral zone (PZ) tumors had higher K1 (p<0.001), and a T/N ratio ≥2 was significant (p<0.001). On DCE MR, the parameters in, kep, Ktrans and quantitative iAUC were higher for PZ and non-PZ tumors than corresponding normal tissue (p<.001); for PZ tumors, a T/N ratio ≥ 1.5 for Ktrans and pei was significant (p=0.0019 and p=0.0026, respectively). Moderate Spearman correlation (0.40<ρ<0.59) was found between dPET K1 and DCE MR Ktrans and pei. Conclusions: In patients with high-risk PCa, quantitative dPET and DCE-MR parameters in primary tumors differ from normal tissue. Only moderate correlation exists between K1 (dPET) and Ktrans and pei (DCE MR). The incremental value of any of these parameters to PI-RADS v2 warrants further investigation. Advances in knowledge: Unique quantitative and semiquantitative FCH PET/MR parameters in PCa differ from normal gland, and should be further investigated to determine their potential contribution to PI-RADS v2 in the detection of clinically significant PCa.
关键词： Magnetic Resonance Imaging,Positron-Emission Tomography,Prostatic Neoplasms,18f-fluoromethylcholine,Adults
更新于2025-09-23 15:21:01
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PET Image Denoising Using a Deep Neural Network Through Fine Tuning
摘要： Positron emission tomography (PET) is a functional imaging modality widely used in clinical diagnosis. In this work, we trained a deep convolutional neural network (CNN) to improve PET image quality. Perceptual loss based on features derived from a pre-trained VGG network, instead of the conventional mean squared error, was employed as the training loss function to preserve image details. As the number of real patient data set for training is limited, we propose to pre-train the network using simulation data and fine-tune the last few layers of the network using real data sets. Results from simulation, real brain and lung data sets show that the proposed method is more effective in removing noise than the traditional Gaussian filtering method.
关键词： Positron emission tomography,fine-tuning,convolutional neural network,perceptual loss,image denoising
更新于2025-09-23 15:21:01
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Preclinical development and first-in-human imaging of the integrin α <sub/>v</sub> β <sub/>6</sub> with [ <sup>18</sup> F]α <sub/>v</sub> β <sub/>6</sub> -Binding Peptide in metastatic carcinoma.
摘要： Purpose: The study was undertaken to develop and evaluate the potential of an integrin αvβ6-binding peptide (αvβ6-BP) for noninvasive imaging of a diverse range of malignancies with positron emission tomography (PET). Experimental Design: The peptide αvβ6-BP was prepared on solid phase and radiolabeled with 4-[18F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using a paired αvβ6-expressing and αvβ6-null cell lines. In vivo evaluation (PET/CT, biodistribution and autoradiography) was performed in a mouse model bearing the same paired αvβ6-expressing and αvβ6-null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast or pancreatic cancer. Results: [18F]αvβ6-BP displayed excellent affinity and selectivity for the integrin in vitro (IC50(αvβ6) = 1.2 nM vsIC50(αvβ3) >10 μM) in addition to rapid target-specific cell binding and internalization (72.5±0.9% binding and 52.5±1.8% respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [18F]αvβ6-BP was rapid, primarily via the kidneys. In patients, [18F]αvβ6-BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [18F]αvβ6-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver and lung. Conclusions: The clinical impact of [18F]αvβ6-BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.
关键词： Positron Emission Tomography,first-in-human,Integrin αvβ6,metastases,peptide
更新于2025-09-23 15:21:01
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Variability and repeatability of quantitative uptake metrics in [ <sup>18</sup> F]FDG PET/CT imaging of non-small cell lung cancer: impact of segmentation method, uptake interval, and reconstruction protocol
摘要： OBJECTIVES: There is increased interest in various new quantitative uptake metrics beyond standardized uptake value (SUV) in oncology PET/CT studies. The purpose of this study is to investigate the variability and test-retest repeatability (TRT) of metabolically active tumor volume (MATV) measurements and several other new quantitative metrics in non-small cell lung cancer (NSCLC) using [18F]FDG PET/CT with different segmentation methods, user interactions, uptake intervals, and reconstruction protocols. METHODS: Ten advanced NSCLC patients received two whole-body [18F]FDG PET/CT scans at both 60 and 90 min post-injection. PET data were reconstructed with four different protocols. Eight segmentation methods were applied to delineate lesions with and without a tumor mask. MATV, maximum and mean SUV (SUVmax, SUVmean), total lesion glycolysis (TLG), and intralesional heterogeneity features were derived. Variability and repeatability were evaluated using a generalized estimating equations statistical model with Bonferroni correction for multiple comparisons. The statistical model, including interaction between uptake interval and reconstruction protocol, was applied individually to the data obtained from each segmentation method. RESULTS: Without masking, none of the segmentation methods could delineate all lesions correctly. MATV was affected by both uptake interval and reconstruction settings for most segmentation methods. Similar observations were obtained for the uptake metrics SUVmax, SUVmean, TLG, homogeneity, entropy, and zone percentage. No effect of uptake interval was observed on TRT metrics, while the reconstruction protocol affected the TRT of SUVmax. Overall, segmentation methods showing poor quantitative performance in one condition showed better performance in other (combined) conditions. For some metrics, a clear statistical interaction was found between the segmentation method and both uptake interval and reconstruction protocol. CONCLUSIONS: All segmentation results need to be reviewed critically. MATV and other quantitative uptake metrics, as well as their TRT, depend on segmentation method, uptake interval, and reconstruction protocol. To obtain quantitative reliable metrics, with good TRT performance, the optimal segmentation method depends on local imaging procedure, the PET/CT system and/or reconstruction protocol. Rigid harmonization of imaging procedure and PET/CT performance will be helpful in mitigating this variability.
关键词： non-small cell lung cancer,segmentation method,positron emission tomography imaging,repeatability,Variability
更新于2025-09-23 15:21:01