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Comparative assessment of linear least-squares, nonlinear least-squares, and Patlak graphical method for regional and local quantitative tracer kinetic modelling in cerebral dynamic <sup>18</sup> F-FDG PET
摘要： Purpose: Dynamic 18F-FDG PET allows quantitative estimation of cerebral glucose metabolism both at the regional and local (voxel) level. Although sensitive to noise and highly computationally expensive, nonlinear least-squares (NLS) optimization stands as the reference approach for the estimation of the kinetic model parameters. Nevertheless, faster techniques, including linear least-squares (LLS) and Patlak graphical method, have been proposed to deal with high resolution noisy data, representing a more adaptable solution for routine clinical implementation. Former research investigating the relative performance of the available algorithms lack precise evaluation of kinetic parameter estimates under realistic acquisition conditions. Methods: The present study aims at the systematic comparison of the feasibility and pertinence of kinetic modelling of dynamic cerebral 18F-FDG PET using NLS, LLS, and Patlak method, based on numerical simulations and patient data. Numerical simulations were used to study and parameters estimation bias and variance under representative noise levels. Patient data allowed to assess the concordance between the three methods at the regional and voxel scale, and to evaluate the robustness of the estimations with respect to patient head motion. Results and Conclusions: Our findings indicate that at the regional level NLS and LLS provide kinetic parameter estimates ( and ) with similar bias and variance characteristics ( bias ± rel. std dev. 0.0±5.1% and 0.1%±4.9% for NLS and LLS respectively, bias ± rel. std dev. 0.1%±4.5% and -0.7%±4.4% for NLS and LLS respectively), NLS estimates being however slightly less sensitive to patient motion. At the voxel level, provided that patient motion is negligible or corrected, LLS offers an appealing alternative solution for local mapping, with high correlation with NLS values (Pearson’s r = 0.95 on actual data) in computations times less than two orders of magnitude lower. Last, Patlak method appears as the most robust and accurate technique for the estimation of values at the regional and voxel scale, with or without head motion. It provides low bias / low variance quantification (bias ± rel. std dev. -1.5±9.5% and -4.1±19.7% for Patlak and NLS respectively) as well as smooth parametric images suitable for visual assessment.
关键词： kinetic analysis,18F-FDG PET,cerebral glucose metabolism,quantification
更新于2025-09-23 15:23:52
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Performance of whole-body 18F-FDG PET/CT as a posttreatment surveillance tool for sinonasal malignancies
摘要： Purpose To determine the diagnostic utility of posttreatment surveillance whole-body 18F-FDG PET/CT in detecting local tumor recurrence (R), regional lymph-node metastasis (LM), and distant metastasis (DM) in asymptomatic sinonasal cancer patients. Methods Eighty consecutive patients (53 men, 27 women; mean age, 60 years; range, 28–92 years) who had undergone 197 posttreatment whole-body 18F-FDG PET/CT examinations for sinonasal malignancies between January 2009 and August 2017 were retrospectively reviewed. 18F-FDG PET/CT findings were categorized as positive or negative for R, LM, and DM, separately. Outcomes of 18F-FDG PET/CT scans were compared with the final diagnosis confirmed by histological analysis or follow-up period for a minimum 12 months. The diagnostic accuracy of scans was calculated for each site using contingency tables. Impact on the management of 18F-FDG PET/CT examinations was additionally evaluated. Results 18F-FDG PET/CT scans identified 37/44 of local recurrences, 21/23 of LMs, and 30/37 of DMs. For local recurrence, sensitivity, specificity, positive predictive value, and negative predictive value were 84% (68–97%), 95% (80–100%), 84% (68–97%), and 95% (80–100%), respectively. For LM, the respective values were 91% (75–100%), 99% (83–100%), 91% (75–100%), and 99% (83–100%). For DM, the values were 81% (64–97%), 99% (85–100%), 97% (81–100%), and 96% (81–100%), respectively. 18F-FDG PET/CT accounted for a change in management of 85% patients with recurrences. Conclusions Whole-body 18F-FDG PET/CT is a suitable surveillance tool for sinonasal malignancies in detecting locoregional and distant recurrences in asymptomatic patients without any evidence of recurrence on regular follow-up and endoscopy during the posttreatment period.
关键词： Posttreatment,Recurrence,Surveillance,Sinonasal malignancies,18F-FDG PET/CT
更新于2025-09-23 15:23:52
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Preclinical evaluation of [ <sup>18</sup> F]MA3, a CB <sub/>2</sub> receptor agonist radiotracer for Positron Emission Tomography
摘要： Background and Purpose: Non-invasive in vivo imaging of CB2 receptors (CB2R) using positron emission tomography (PET) is pursued to study neuroinflammation. The purpose of this study is to evaluate the in vivo binding specificity of [18F]MA3, a CB2R agonist, in a rat model with local overexpression of human CB2R (hCB2R). Methods: [18F]MA3 was produced with good radiochemical yield and radiochemical purity. The radiotracer was evaluated in rats with local overexpression of hCB2R and in a healthy non-human primate using PET. Key results: Ex vivo autoradiography demonstrated CB2 specific binding of [18F]MA3 in rat hCB2R vector injected striatum. In a PET study, increased tracer binding in the hCB2R vector injected striatum compared to the contralateral control vector injected striatum was observed. Binding in hCB2R vector injected striatum was blocked with a structurally non related CB2R inverse agonist and a displacement study confirmed the reversibility of tracer binding. This study identified the utility of mutated inactive vector model for evaluation of CB2R agonist PET tracers. [18F]MA3 PET scans in the non-human primate showed good uptake and fast wash out from brain, but no CB2 specific binding was observed. Conclusion and Implications: Evaluation of [18F]MA3 in a rat model with local overexpression of hCB2R showed CB2 specific and reversible tracer binding. [18F]MA3 showed good brain uptake and subsequent wash out in a healthy non-human primate but no specific binding was observed. Further clinical evaluation of [18F]MA3 in patients with neuroinflammation is warranted.
关键词： CB2R,PET imaging,neuroinflammation,[18F]MA3,radiotracer
更新于2025-09-23 15:22:29
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PET-Liganden für die Diagnostik der Alzheimer-Demenz: Amyloid und Tau
摘要： Over the last 15 years diagnostic imaging of amyloid and tau deposits with PET has gained increasing importance especially in the context of diagnosis of dementia such as Alzheimer's disease. First radiotracers that were developed aimed at the detection of amyloid plaques in the brain. In the meantime the contribution of hyperphosphorylated proteins (TAU) that lead to another type of protein deposits is getting more and more in the focus of current research on the origin of this disease. While a number of 18F-labelled ligands for amyloid imaging have recently been granted marketing authorization and therefore are commercially available and can be used by licensed nuclear medicine physicians throughout Europe and the US, this is not true for radiotracers for TAU-protein imaging. Therefore their use is restricted to clinical trials or to the application of in house manufactured substances. This article should give an overview on characteristics, development and availability of PET tracers for amyloid and tau imaging and in addition to that exemplify the challenges associated with a GMP compliant manufacturing of these short lived radiotracers.
关键词： Alzheimer,18F,Amyloid,11C,PET,Tau
更新于2025-09-23 15:22:29
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18F?alfatide positron emission tomography may predict anti?angiogenic responses
摘要： As the crucial issue in the development of anti-angiogenic drugs is how to predict which patients will and will not benefit prior to the initiation of therapy, angiogenic 18F-alfatide positron emission computed tomography (PET) was assessed in the present study. Lung adenocarcinoma A549 (high angiogenesis) and prostate PC?3 (low angiogenesis) cell xenografted tumor-bearing mice underwent 18F-alfatide PET at baseline and following treatment with either an anti?angiogenic therapy or vehicle. The evaluation index for the inhibition of tumor growth in the individuals in the treated groups was represented by treatment/control (T/C) ratio (%). Anti?angiogenic responses were denoted by the changes in 18F-alfatide uptake in the same animal. The T/C ratio was lower in high-uptake tumors than in low?uptake tumors (P=0.001). A significant difference in the tumor volumes between the anti?angiogenic therapy group and the control group occurred earlier in the A549 model than in the PC?3 model. 18F-alfatide uptake decreased more for A549 tumors than for PC?3 tumors following anti?angiogenic therapy. In each treatment group, the degree of tumor response to anti?angiogenic therapy was associated well with the tumor uptake prior to treatment (P<0.05). These results indicated that 18F?alfatide PET may be a useful molecular imaging tool for individual selection prior to anti?angiogenic drug therapy.
关键词： 18F?alfatide positron emission tomography,heterogeneity,integrin αvβ3,response prediction,anti?angiogenic therapy
更新于2025-09-23 15:22:29
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PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation
摘要： Purpose: The P2X7 receptor, an adenosine triphosphate (ATP)-gated purinoreceptor, has emerged as one of the key players in neuroinflammatory processes. Therefore, developing a positron emission tomography (PET) tracer for imaging of P2X7 receptors in vivo presents a promising approach to diagnose, monitor, and study neuroinflammation in a variety of brain disorders. To fulfill the goal of developing a P2X7 PET ligand as a biomarker of neuroinflammation, [18F]JNJ-64413739 has been recently disclosed. Procedures: We evaluated [18F]JNJ-64413739 in a rat model of neuroinflammation induced by an intracerebral injection of lipopolysaccharide (LPS). In vivo brain uptake was determined by PET imaging. Upregulation of neuroinflammatory biomarkers was determined by quantitative polymerase chain reaction (qPCR). Distribution of the tracer in the brain was determined by ex vivo autoradiography (ARG). The specificity of [18F]JNJ-64413739 was confirmed by performing blocking experiments with the P2X7 antagonist JNJ-54175446. Results: Brain regions of rats injected with LPS had a significantly increased uptake (34 % ± 3 % s.e.m., p = 0.036, t test, standardized uptake value measured over the entire scanning period) of [18F]JNJ-64413739 relative to the corresponding brain regions of control animals injected with phosphate-buffered saline (PBS). The uptake in the contralateral regions and cerebellum was not significantly different between the groups of animals. The increase in uptake of [18F]JNJ-64413739 at the LPS-injected site observed by PET imaging was concordant with ex vivo ARG, upregulation of neuroinflammatory biomarkers, and elevated P2X7 expression levels. Conclusions: While further work is needed to study [18F]JNJ-64413739 in other types of neuroinflammation, the current results favorably characterize [18F]JNJ-64413739 as a potential PET tracer of central neuroinflammation.
关键词： Lipopolysaccharide,Rats,Positron emission tomography (PET),PET imaging,P2X7 receptor,LPS,[18F]JNJ-64413739,Neuroinflammation
更新于2025-09-23 15:22:29
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18F-FDG PET/TC para la estadificación y la delineación del volumen de radioterapia en el cáncer de cabeza y cuello
摘要： Purpose: The aim is to investigate the use of 18F-FDG (fluorine-18 fluorodeoxyglucose) PET/CT in head and neck cancer (HNC) staging and its effect on the therapeutic strategy and radiotherapy (RT) planning. Methods and materials: One hundred patients with HNC were included. Primary tumor sites: 18% oral cavity, 20% oropharynx, 12% hypopharynx, 11% nasopharynx, 37% larynx, 2% paranasal sinuses. Patients were staged according to the American Joint Committee of Cancer 7th edition. Stage: 5% stage I, 7% stage II, 14% stage III, 61% stage IVA, 7% stage IVB and 6% stage IVC. A contrast-enhanced CT and a 18F-FDG PET/CT acquired under RT position were performed. Both exams were compared to analyze patients' staging reclassification. Changes in therapeutic strategy were analyzed. Results: 18F-FDG PET/CT detected 6 distant metastases and treatment intention changed to palliative. Eight synchronous tumors were detected; one received palliative treatment. 18F-FDG PET/CT reclassified cTNM staging in 27 patients. Tumor extension changed in 28 (14% up-staged; 14% down-staged), implying a change in GTV (Gross Tumor Volume) delineation. Nodal detection was reclassified in 47 patients: 8 patients down-staged (N2C to N2A/N2B/N1) and 2 were false positive. Nineteen patients were false negatives and 5 staged as N+ (N1/N2A/N2B) turned out into N2C. These staging modifications imply adapting the nodal volume to be irradiated. Conclusions: 18F-FDG PET/CT reclassification was higher than 10% in almost all categories studied (cTNM, tumor extension and nodal disease) and detects more metastases and synchronous tumors than conventional studies, which has an impact on the therapeutic patient management and RT planning.
关键词： Head and neck cancer,18F-FDG PET/CT,Radiotherapy planning,Staging
更新于2025-09-23 15:22:29
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Primary Pulmonary Low-Grade Angiosarcoma Characterized by Mismatch between <sup>18</sup> F-FDG PET and Dynamic Contrast-Enhanced CT
摘要： We report a rare case of primary pulmonary low-grade angiosarcoma on dynamic contrast-enhanced CT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging. A 38-year-old, asymptomatic woman was hospitalized because of an abnormality on chest radiography. A dynamic contrast-enhanced chest CT showed a 1.2 cm-sized irregular-margined nodule with strong and persistent enhancement in the right lower lobe. The lesion had low metabolic activity on an 18F-FDG PET/CT scan. The patient underwent a wedge resection for the lesion, and pathology revealed a primary pulmonary low-grade angiosarcoma.
关键词： Primary pulmonary angiosarcoma,Dynamic contrast-enhanced CT,Low-grade,18F-FDG PET/CT
更新于2025-09-23 15:22:29
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Low-Dose PET/CT and Full-Dose Contrast-Enhanced CT at the Initial Staging of Localized Diffuse Large B-Cell Lymphomas
摘要： Computed tomography (CT) has been used as the reference imaging technique for the initial staging of diffuse large B-cell lymphoma until recent days, when the introduction of positron emission tomography (PET)/CT imaging as a hybrid technique has become of routine use. However, the performance of both examinations is still common. The aim of this work was to compare the findings between low-dose 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) PET/CT and full-dose contrast-enhanced CT (ceCT) in 28 patients with localized diffuse large B-cell lymphoma according to PET/CT findings, in order to avoid the performance of ceCT. For each technique, a comparison in the number of nodal and extranodal involved regions was performed. PET/CT showed more lesions than ceCT in both nodal (41 vs. 36) and extranodal localizations (16 vs. 15). Disease staging according to both techniques was concordant in 22 patients (79%) and discordant in 6 patients (21%), changing treatment management in 3 patients (11%). PET/CT determined a better staging and therapeutic approach, making the performance of an additional ceCT unnecessary.
关键词： 18F-FDG,staging,positron emission tomography/computed tomography,diffuse large B-cell lymphoma
更新于2025-09-23 15:22:29
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Synthesis and <i>in vivo</i> evaluation of a novel PET radiotracer for imaging of synaptic vesicle glycoprotein 2A (SV2A) in non-human primates
摘要： Structural disruption and alterations of synapses are associated with many brain disorders, including Alzheimer’s disease, epilepsy, depression and schizophrenia. We have previously developed the PET radiotracer 11C-UCB-J for imaging and quantification of synaptic vesicle glycoprotein 2A (SV2A) and synaptic density in non-human primates and humans. Here we report the synthesis of a novel radiotracer 18F-SDM-8 and its in vivo evaluation in rhesus monkeys. The in vitro binding assay of SDM-8 showed high SV2A binding affinity (Ki = 0.58 nM). 18F-SDM-8 was prepared in high molar activity (241.7 MBq/nmol) and radiochemical purity (> 98%). In the brain, 18F-SDM-8 displayed very high uptake with peak standardized uptake value greater than 8, and fast and reversible kinetics. A displacement study with levetiracetam and blocking studies with UCB-J and levetiracetam demonstrated its binding reversibility and specificity towards SV2A. Regional binding potential values were calculated and ranged from 0.8 in the brainstem to 4.5 in the cingulate cortex. Comparing to 11C-UCB-J, 18F-SDM-8 displayed the same attractive imaging properties: very high brain uptake, appropriate tissue kinetics, and high levels of specific binding. Given the longer half-life of F-18 and the feasibility for central production and multi-site distribution, 18F-SDM-8 holds promise as an excellent radiotracer for SV2A and as a biomarker for synaptic density measurement in neurodegenerative diseases and psychiatric disorders.
关键词： UCB-J,18F-SDM-8,PET,SV2A,non-human primates,synaptic density
更新于2025-09-23 15:21:21