Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play...Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinfammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid （Poly I：C） during pregnancy using ^11C-PK11195 positron emission tomography （PET） and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats.Methods Offspring of Poly I：C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition （PPI） and latent inhibition （LI） test （including active avoidance conditioning task and passive avoidance conditioning task）. Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and defcits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex （t=-3.990, p=0.003） and hippocampus （t=-4.462, p=0.001）. The number of activated microglia cells was signifcantly higher in the treatment group than in the control group （hippocampus： t=8.204, p〈0.001; prefrontal： t=6.995, p〈0.001）. Within the treatment group, there were signifcant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.Conclusions The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.展开更多
Abnormal Tau deposition is a crucial pathological hallmark of various neurodegenerative disorders defined as tauopathies,of which Alzheimer’s disease is the most prominent one.To date,a large number of chemical entit...Abnormal Tau deposition is a crucial pathological hallmark of various neurodegenerative disorders defined as tauopathies,of which Alzheimer’s disease is the most prominent one.To date,a large number of chemical entities with different structures have been developed as Tau imaging tracers for the early diagnosis of tauopathies.Several of them with excellent bio-properties are currently being assessed in clinical trials,and more recently,the Tauvid^(TM)([^(18)F]Flortaucipir,also known as[^(18)F]AV1451 or[^(18)F]T807)as the first Tau tracer was approved by the U.S.Food and Drug Administration in 2020.This review summarized the latest development of Tau tracers and analyzed their chemical structures,with particular attention to the effects of chemical structures on biological properties.In addition,we also discuss the limitations of current Tau imaging tracers,issues that need attention in the development of new tracers,and possible future directions.展开更多
Over the past two decades, the development of functional imaging methods has greatly promoted our understanding on the changes of neurons following neurodegenerative disorders, such as Parkin- son＇s disease （PD）. T...Over the past two decades, the development of functional imaging methods has greatly promoted our understanding on the changes of neurons following neurodegenerative disorders, such as Parkin- son＇s disease （PD）. The application of a spatial covariance analysis on 18F-FDG PET imaging has led to the identification of a distinc- tive disease-related metabolic pattern. This pattern has proven to be useful in clinical diagnosis, disease progression monitoring as well as assessment of the neuronal changes before and after clinical treatment. It may potentially serve as an objective biomarker on disease progression monitoring, assessment, histological and func- tional evaluation of related diseases.展开更多
Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically relev...Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically relevant.We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography(PET)ATN biomarkers in subjects with cognitive complaints.Methods A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging(18F-florbetapir for A,18F-Florzolotau for T,and 18F-fluorodeoxyglucose[18F-FDG]for N)was enrolled(n=137).Theβ-amyloid(Aβ)status(positive versus negative)and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances.Results Plasma phosphorylated tau 181(p-tau181)level was found to be associated with PET imaging of ATN biomarkers in the entire cohort.Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+and Aβ−subjects.An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+subjects.Additionally,glucose hypometabolism-along with elevated plasma neurofilament light chain level-was related to more severe cognitive impairment in Aβ−subjects.Conclusion Plasma p-tau181,as well as 18F-florbetapir and 18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβstatus in symptomatic stages of AD.18F-Florzolotau and 18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment.Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.展开更多
This Bombesin (BBN), a tetradecapeptide analog of human gastrin-releasing peptide (GRP) with a high binding affinity for GRP receptors (GRPR), is over- expressed in early stages of androgen-dependent prostate carcinom...This Bombesin (BBN), a tetradecapeptide analog of human gastrin-releasing peptide (GRP) with a high binding affinity for GRP receptors (GRPR), is over- expressed in early stages of androgen-dependent prostate carcinomas, but not in advanced stages. Therefore, there is a need to develop effective tracers for the accurate and specific detection of this disease. The objective of this study was to evaluate Lys<sup>1</sup>, Lys<sup>3</sup>-DOTA-BBN (1,14) analog with the radiolabeled positron emitter [<sup>68</sup>Ga]-Ga-BBN for receptor imaging with PET, and to determine its biodistribution and radiation dosimetry using whole-body (WB) PET scans in healthy volunteers. The highest uptake was in the pancreas, followed by urinary bladder. The critical organ was pancreas with a mean absorbed dose of 206 ± 0.7, 210 ± 0.7, 120 ± 0.9, 390.23 ± 0.6 μGy/MBq and the effective doses were estimated as 73.2 ± 0.6, 49.8 ± 0.3 μGy/MBq (women and men, respectively).展开更多
The development of peptide-based,radiometal-labeled PET imaging agents has seen an increase in attention due to the favorable properties the peptide backbone exhibits.These include high selectivity and affinity to pro...The development of peptide-based,radiometal-labeled PET imaging agents has seen an increase in attention due to the favorable properties the peptide backbone exhibits.These include high selectivity and affinity to proteins and cells directly linked to various types of cancers.In addition,rapid clearance from circulation and low toxicity allow for unique approaches to engineering a viable peptide-based imaging agent.Utilizing peptides as the backbone allows for various modifications to improve metabolic stability,target cell affinity,and image quality and imaging capabilities and reduce toxicity.Select radiolabeled peptides have already been FDA approved,with many more in late-stage trials.This review summarizes the current state of the radiometal-labeled PET peptide imaging field as well as explores methods used by researchers to modify peptides,concluding with a look at the future of peptide-based therapy and diagnostics.展开更多
Background With bipolar disorder(BD)having a lifetime prevalence of 4.4%and a significant portion of patients being chronically burdened by symptoms,there has been an increased focus on uncovering new targets for inte...Background With bipolar disorder(BD)having a lifetime prevalence of 4.4%and a significant portion of patients being chronically burdened by symptoms,there has been an increased focus on uncovering new targets for intervention in BD.One area that has shown early promise is the mitochondrial hypothesis.However,at the time of publication no studies have utilized positron emission tomography(PET)imaging to assess mitochondrial function in the setting of BD.Case Presentation Our participant is a 58 year-old male with a past medical history notable for alcohol use disorder and BD(unspecified type)who underwent PET imaging with the mitochondrial complex I PET ligand^(18)F-BCPP-EF.The resulting images demonstrated significant overlap between areas of dysfunction identified with the^(18)F-BCPP-EF PET ligand and prior functional magnetic resonance imaging(MRI)techniques in the setting of BD.That overlap was seen in both affective and cognitive circuits,with mitochondrial dysfunction in the fronto-limbic,ventral affective,and dorsal cognitive circuits showing particularly significant differences.Conclusions Despite mounting evidence implicating mitochondria in BD,this study represents the first PET imaging study to investigate this mechanistic connection.There were key limitations in the form of comorbid alcohol use disorder,limited statistical power inherent to a case study,no sex matched controls,and the absence of a comprehensive psychiatric history.However,even with these limitations in mind,the significant overlap between dysfunction previously demonstrated on functional MRI and this imaging provides compelling preliminary evidence that strengthens the mechanistic link between mitochondrial dysfunction and BD.展开更多
Background:The chicken chorioallantoic membrane(CAM)model is a potential alter-native to the mouse model based on the 3R principles.However,its value for deter-mination of the in vivo behaviors of radiolabeled peptide...Background:The chicken chorioallantoic membrane(CAM)model is a potential alter-native to the mouse model based on the 3R principles.However,its value for deter-mination of the in vivo behaviors of radiolabeled peptides through positron emission tomography(PET)imaging needed investigation.Herein,the chicken CAM tumor models were established,and their feasibility was evaluated for evaluating the imag-ing properties of radiolabeled peptides using a 68Ga-labeled HER2 affibody.Methods:Two human breast cancer cell lines were inoculated into chicken CAM and mice,respectively.The tumor-targeting potential and pharmacokinetic profile of a 68Ga-labeled affibody,68Ga-MZHER,in both tumor models were also determined.Results:The tumor-formation time in chicken CAM model was shorter than that of mouse model.The uptake values of human epithelial growth factor receptor-2(HER2)-positive Bcap37 tumors in chicken CAM and mouse models were 5.36±0.26%ID/g and 5.26±0.43%ID/g at 30 min postinjection of 68Ga-MZHER,respectively.At the same time points,the uptake values of HER2-negative MDA-MB-231 tumors in the chicken CAM models and mouse models were 1.57±0.15%ID/g and 1.67±0.25%ID/g,respectively.Ex vivo biodistribution confirmed that more radioactivity accu-mulated in Bcap37 tumors than in MDA-MD-231 tumors in both CAM and mouse models.Conclusion:In this study,the CAM tumor model was successfully prepared.The chicken CAM model is a novel tool for quickly determining the in vivo properties of radiolabeled peptides targeting biomarkers.It may be beneficial for early monitoring of the therapeutic effect of a new drug through PET imaging with specific peptides.展开更多
The segmentation of head and neck(H&N)tumors in dual Positron Emission Tomography/Computed Tomogra-phy(PET/CT)imaging is a critical task in medical imaging,providing essential information for diagnosis,treatment p...The segmentation of head and neck(H&N)tumors in dual Positron Emission Tomography/Computed Tomogra-phy(PET/CT)imaging is a critical task in medical imaging,providing essential information for diagnosis,treatment planning,and outcome prediction.Motivated by the need for more accurate and robust segmentation methods,this study addresses key research gaps in the application of deep learning techniques to multimodal medical images.Specifically,it investigates the limitations of existing 2D and 3D models in capturing complex tumor structures and proposes an innovative 2.5D UNet Transformer model as a solution.The primary research questions guiding this study are:(1)How can the integration of convolutional neural networks(CNNs)and transformer networks enhance segmentation accuracy in dual PET/CT imaging?(2)What are the comparative advantages of 2D,2.5D,and 3D model configurations in this context?To answer these questions,we aimed to develop and evaluate advanced deep-learning models that leverage the strengths of both CNNs and transformers.Our proposed methodology involved a comprehensive preprocessing pipeline,including normalization,contrast enhancement,and resampling,followed by segmentation using 2D,2.5D,and 3D UNet Transformer models.The models were trained and tested on three diverse datasets:HeckTor2022,AutoPET2023,and SegRap2023.Performance was assessed using metrics such as Dice Similarity Coefficient,Jaccard Index,Average Surface Distance(ASD),and Relative Absolute Volume Difference(RAVD).The findings demonstrate that the 2.5D UNet Transformer model consistently outperformed the 2D and 3D models across most metrics,achieving the highest Dice and Jaccard values,indicating superior segmentation accuracy.For instance,on the HeckTor2022 dataset,the 2.5D model achieved a Dice score of 81.777 and a Jaccard index of 0.705,surpassing other model configurations.The 3D model showed strong boundary delineation performance but exhibited variability across datasets,while the 2D model,although effective,generally underperformed compared to its 2.5D and 3D counterparts.Compared to related literature,our study confirms the advantages of incorporating additional spatial context,as seen in the improved performance of the 2.5D model.This research fills a significant gap by providing a detailed comparative analysis of different model dimensions and their impact on H&N segmentation accuracy in dual PET/CT imaging.展开更多
Bladder tumor is the most common malignant tumor in urinary system and always com- panied with lymph node metastasis. The accurate staging plays a significant role in treatment for bladder tumor and prognostic evaluat...Bladder tumor is the most common malignant tumor in urinary system and always com- panied with lymph node metastasis. The accurate staging plays a significant role in treatment for bladder tumor and prognostic evaluation, and the distant metastasis predicts worse prognosis. The objective of this study was to assess the clinical significance of 18F-FDG PET/CT imaging in diagnosing bladder tumor metastasis lesions. A retrospective analysis of 60 patients with bladder tumor from October 2008 to May 2010 was done. The patients were stratified based on the imaging technique. Among all 60 cases, besides the primary lesion, 81 suspected lesions were spotted and 73 confirmed as metastasis, including 50 lymph node metastases, 22 distant metastases, and 1 bone metastasis. For PET/CT imaging, its sensitivity was 94.5%, specificity 87.5%, positive predictive value 98.6%, negative predictive value 63.6% and accuracy 93.8% respectively. For CT, its sensitivity was 82.2%, specificity 50%, positive predictive value 93.8%, negative predictive value 23.5% and accuracy 79% respectively. PET/CT im- aging was superior to CT in sensitivity, specificity and accuracy. In conclusion, 18F-FDG PET/CT imaging is more significant in diagnosing bladder tumor metastasis lesions.展开更多
The cause of obstructive jaundice is usually complex which renders its differential diagnosis and lesion localization challenging in clinical practice.Integrated Positron Emission tomography/Magnetic Resonance(PET/MR)...The cause of obstructive jaundice is usually complex which renders its differential diagnosis and lesion localization challenging in clinical practice.Integrated Positron Emission tomography/Magnetic Resonance(PET/MR)offers complementary information from PET and MR in the diagnosis of obstructive jaundice and is becoming widely adopted in clinical setting.While preserving its diagnostic accuracy,it is important to standardize and streamline the clinical scan protocol of PET/MR in evaluating obstructive jaundice.Based on literature review and experience of large number of clinical cases from the author group,this article reports an expert consensus on imaging protocol optimization and case interpretation template standardization.展开更多
Diabetes and insulinoma represent opposing alterations in pancreatic β-cell mass,with diabetes resulting from irreversible β-cells damage and insulinoma arising from abnormal proliferation.Early diagnosis of both co...Diabetes and insulinoma represent opposing alterations in pancreatic β-cell mass,with diabetes resulting from irreversible β-cells damage and insulinoma arising from abnormal proliferation.Early diagnosis of both conditions necessitates effectiveβ-cell mass detection.Current detection methods are limited in diagnosing each condition individually or lacking timely and accurate detection.Diabetes is typically identified only after significantβ-cell loss,while insulinoma can evade conventional imaging due to their small size.Positron emission tomography/computed tomography(PET/CT)imaging,combining anatomical and functional data,enhances diagnostic accuracy but faces challenges in specificity.This study employed two RNA aptamers(m12–3773 and 1–717)modified to enhance RNase resistance and conjugated with68Ga to create ^(68)Ga-NOTA-Ap.^(68)Ga-NOTA-Ap was administered to rats with pancreaticβ-cell damage and mice with insulinoma to evaluate its ability to image islets,detect changes in pancreatic β-cell mass(BCM),and identify insulinoma.Modified with methoxy and fluoro,RNA aptamers exhibited enhanced stability and RNases resistance while retaining their dissociation constants(K_(d)).Furthermore,^(68)Ga-NOTA-Ap effectively detected changes of BCM in rats with pancreatic β-cell damage and imaged insulinoma in mice through recognition of abnormalβ-cell proliferation by recognizing clusterin and transmembrane p24 trafficking protein 6(TMED6)on pancreaticβ-cell.The developed ^(68)Ga-NOTA-Ap shows promise for early screening of diabetes and insulinoma due to its high sensitivity,specificity,and non-invasive nature.It has potential clinical applications for monitoring pancreatic β-cell function and diagnosing insulinoma.展开更多
Polyamine metabolism dysregulation is a hallmark of many cancers,offering a promising avenue for early tumor theranostics.This study presents the development of a nuclear probe derived from spermidine(SPM)for dual-pur...Polyamine metabolism dysregulation is a hallmark of many cancers,offering a promising avenue for early tumor theranostics.This study presents the development of a nuclear probe derived from spermidine(SPM)for dual-purpose tumor PET imaging and internal radiation therapy.The probe,radiolabeled with either[68Ga]Ga for diagnostic applications or[177Lu]Lu for therapeutic use,was synthesized with exceptional purity,stability,and specific activity.Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells,showcasing outstanding tumor localization and target-to-non-target ratio.Mechanistic investigations employing polyamines,non-labeled precursor,and polyamine transport system(PTS)inhibitor,consistently affirmed the probe?s targetability through recognition of the PTS.Notably,while previous reports indicated PTS upregulation in various tumor types for targeted therapy,this study observed no positive signals,highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis.Furthermore,when labeled with[177Lu],the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival.Investigations into biodistribution,excretion,and biosafety in healthy humans laid a robust foundation for clinical translation.This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics,offering promising prospects for clinical implementation.展开更多
The precise detection and segmentation of tumor lesions are very important for lung cancer computer-aided diagnosis.However,in PET/CT(Positron Emission Tomography/Computed Tomography)lung images,the lesion shapes are ...The precise detection and segmentation of tumor lesions are very important for lung cancer computer-aided diagnosis.However,in PET/CT(Positron Emission Tomography/Computed Tomography)lung images,the lesion shapes are complex,the edges are blurred,and the sample numbers are unbalanced.To solve these problems,this paper proposes a Multi-branch Cross-scale Interactive Feature fusion Transformer model(MCIF-Transformer Mask RCNN)for PET/CT lung tumor instance segmentation,The main innovative works of this paper are as follows:Firstly,the ResNet-Transformer backbone network is used to extract global feature and local feature in lung images.The pixel dependence relationship is established in local and non-local fields to improve the model perception ability.Secondly,the Cross-scale Interactive Feature Enhancement auxiliary network is designed to provide the shallow features to the deep features,and the cross-scale interactive feature enhancement module(CIFEM)is used to enhance the attention ability of the fine-grained features.Thirdly,the Cross-scale Interactive Feature fusion FPN network(CIF-FPN)is constructed to realize bidirectional interactive fusion between deep features and shallow features,and the low-level features are enhanced in deep semantic features.Finally,4 ablation experiments,3 comparison experiments of detection,3 comparison experiments of segmentation and 6 comparison experiments with two-stage and single-stage instance segmentation networks are done on PET/CT lung medical image datasets.The results showed that APdet,APseg,ARdet and ARseg indexes are improved by 5.5%,5.15%,3.11%and 6.79%compared with Mask RCNN(resnet50).Based on the above research,the precise detection and segmentation of the lesion region are realized in this paper.This method has positive significance for the detection of lung tumors.展开更多
Reactive oxygen species(ROS)are involved in the onset and development of neurodegenerative diseases,such as Alzheimer's disease(AD)and Parkinson's disease(PD).Hydrogen peroxide(H_(2)O_(2)),a key type of ROS,is...Reactive oxygen species(ROS)are involved in the onset and development of neurodegenerative diseases,such as Alzheimer's disease(AD)and Parkinson's disease(PD).Hydrogen peroxide(H_(2)O_(2)),a key type of ROS,is overexpressed in the early stages of AD and PD and is involved in the disease progression.Assessing H_(2)O_(2) levels in the brain is considered to be a valuable tool for detecting neurodegenerative diseases and exploring their pathogenesis.In this study,we developed two self-immobilizing PET tracers([^(18)F]HYAS and[^(18)F]HYAT)based on a quinone methide(QM)scaffold for non-invasive imaging of H_(2)O_(2) in the brain.Both tracers can respond to H_(2)O_(2) by forming a QM intermediate,which rapidly reacts with nucleophiles.[^(18)F]HYAT,with proper physicochemical properties,is able of crossing the blood-brain barrier.Increased uptake of[^(18)F]HYAT was observed in the brains of mice treated with 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine(MPTP),indicating that[^(18)F]HYAT is a useful tracer for PET imaging of H_(2)O_(2) in the brain.展开更多
Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography(PET)for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-t...Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography(PET)for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b,are synthesized.The triflate agent,9a or 9b,is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine,protection of the amine group with di-tert-butyl dicarbonate,alkylation with chlorohydrin,and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 30%and 15%,respectively.展开更多
Although the epigenetic regulatory protein histone deacetylase 6(HDAC6)has been recently implicated in the etiology of Alzheimer’s disease(AD),little is known about the role of HDAC6 in the etiopathogenesis of AD and...Although the epigenetic regulatory protein histone deacetylase 6(HDAC6)has been recently implicated in the etiology of Alzheimer’s disease(AD),little is known about the role of HDAC6 in the etiopathogenesis of AD and whether HDAC6 can be a potential therapeutic target for AD.Here,we performed positron emission tomography(PET)imaging in combination with histopathological analysis to better understand the underlying pathomechanisms of HDAC6 in AD.We first developed[^(18)F]PB118 which was demonstrated as a valid HDAC6 radioligand with excellent brain penetration and high specificity to HDAC6.PET studies of[^(18)F]PB118 in 5xFAD mice showed significantly increased radioactivity in the brain compared to WT animals,with more pronounced changes identified in the cortex and hippocampus.The translatability of this radiotracer for AD in a potential human use was supported by additional studies,including similar uptake profiles in non-human primates,an increase of HDAC6 in ADrelated human postmortem hippocampal tissues by Western blotting protein analysis,and our ex vivo histopathological analysis of HDAC6 in postmortem brain tissues of our animals.Collectively,our findings show that HDAC6 may lead to AD by mechanisms that tend to affect brain regions particularly susceptible to AD through an association with amyloid pathology.展开更多
^(11)C-PK11195 is a positron emitter tracer used for Positron Emission Tomography(PET)imaging of innate immune cell activation in studies of neuroinflammatory diseases.For the image quantitative analysis,it is necessa...^(11)C-PK11195 is a positron emitter tracer used for Positron Emission Tomography(PET)imaging of innate immune cell activation in studies of neuroinflammatory diseases.For the image quantitative analysis,it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition(plasma intact fraction).Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition.The purpose of this study is to compare 11CPK11195 plasma metabolization rate between healthy controls and multiple sclerosis(MS)patients and evaluate the interference of sex,age,treatment,and disease phenotype in the tracer intact fraction measured in arterial plasma samples.11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients(n=50)and healthy controls(n=23)at 20,45,and 60 minutes after 11C-PK11195 injection.Analyses were also stratified by sex,age,treatment type,and MS phenotype.The results showed no significant differences in the metabolization rate of healthy controls and MS patients,or in the stratified samples.In conclusion,11C-PK11195 metabolization has the same rate in patients with MS and healthy controls,which is not affected by sex,age,treatment,and disease phenotype.Thus,these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition,by using a population metabolization rate average.The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School(approval No.624.065)on April 23,2014.展开更多
In animal experiments,ischemic stroke is usually induced through middle cerebral artery occlusion(MCAO),and quality assessment of this procedure is crucial.However,an accurate assessment method based on 18F-fluorodeox...In animal experiments,ischemic stroke is usually induced through middle cerebral artery occlusion(MCAO),and quality assessment of this procedure is crucial.However,an accurate assessment method based on 18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)is still lacking.The difficulty lies in the inconsistent preprocessing pipeline,biased intensity normalization,or unclear spatiotemporal uptake of FDG.Here,we propose an image feature-based protocol to assess the quality of the procedure using a 3D scale-invariant feature transform and support vector machine.This feature-based protocol provides a convenient,accurate,and reliable tool to assess the quality of the MCAO procedure in FDG PET studies.Compared with existing approaches,the proposed protocol is fully quantitative,objective,automatic,and bypasses the intensity normalization step.An online interface was constructed to check images and obtain assessment results.展开更多
1-[^18F]Fluoro-l-deoxy-2,5-anhydro-D-mannitol （3, ^18F-FDAM） has been synthesized in 6 steps starting from 2,5-anhydro-D-mannitol （2,5-AM） and evaluated as a new radiotracer for PET imaging of MCF-7 breast tumor. ...1-[^18F]Fluoro-l-deoxy-2,5-anhydro-D-mannitol （3, ^18F-FDAM） has been synthesized in 6 steps starting from 2,5-anhydro-D-mannitol （2,5-AM） and evaluated as a new radiotracer for PET imaging of MCF-7 breast tumor. The result of PET imaging study showed that 3 displayed a slightly higher uptake by breast tumor in comparison with the normal breast tissue, implying the possibility of development of PET radiotraeers based on targeting fructose transporters.展开更多
基金provided by the National Natural Science Foundation of China(No 81571318 to XQSNo 81371472 to LXL+5 种基金No 81401110 to XL)the Science and Technology Planning Project of Health and Family Planning Commission(No 201501015 to XQS)the International Science and Technology Cooperation Program of Henan(No 162102410061 to XQS)the Henan Province Union Fund Project(162300410275)the Zhengzhou University doctor team projectthe Youth Fund of the First Affiliated Hospital of Zhengzhou University(to XL and LJP)
文摘Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinfammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid （Poly I：C） during pregnancy using ^11C-PK11195 positron emission tomography （PET） and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats.Methods Offspring of Poly I：C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition （PPI） and latent inhibition （LI） test （including active avoidance conditioning task and passive avoidance conditioning task）. Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and defcits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex （t=-3.990, p=0.003） and hippocampus （t=-4.462, p=0.001）. The number of activated microglia cells was signifcantly higher in the treatment group than in the control group （hippocampus： t=8.204, p〈0.001; prefrontal： t=6.995, p〈0.001）. Within the treatment group, there were signifcant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.Conclusions The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.
基金funded by the National Natural Science Foundation of China(Nos.U1967221,22022601)。
文摘Abnormal Tau deposition is a crucial pathological hallmark of various neurodegenerative disorders defined as tauopathies,of which Alzheimer’s disease is the most prominent one.To date,a large number of chemical entities with different structures have been developed as Tau imaging tracers for the early diagnosis of tauopathies.Several of them with excellent bio-properties are currently being assessed in clinical trials,and more recently,the Tauvid^(TM)([^(18)F]Flortaucipir,also known as[^(18)F]AV1451 or[^(18)F]T807)as the first Tau tracer was approved by the U.S.Food and Drug Administration in 2020.This review summarized the latest development of Tau tracers and analyzed their chemical structures,with particular attention to the effects of chemical structures on biological properties.In addition,we also discuss the limitations of current Tau imaging tracers,issues that need attention in the development of new tracers,and possible future directions.
基金supported by grants from the China-US Biomedical Collaborative Research Program(No.81361120393)the National Foundation of Natural Science of China(No.81171189)
文摘Over the past two decades, the development of functional imaging methods has greatly promoted our understanding on the changes of neurons following neurodegenerative disorders, such as Parkin- son＇s disease （PD）. The application of a spatial covariance analysis on 18F-FDG PET imaging has led to the identification of a distinc- tive disease-related metabolic pattern. This pattern has proven to be useful in clinical diagnosis, disease progression monitoring as well as assessment of the neuronal changes before and after clinical treatment. It may potentially serve as an objective biomarker on disease progression monitoring, assessment, histological and func- tional evaluation of related diseases.
基金supported by grants from the National Natural Science Foundation of China(81971641,82071200,82272039,and 82021002)the STI2030-Major Project(2022ZD0211600)+2 种基金the Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1038B,SHDC2020CR4007)the National Key R&D Program of China(2022YFC2009902,2022YFC2009900)Medical Innovation Research Project of Shanghai Science and Technology Commission(21Y11903300).
文摘Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically relevant.We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography(PET)ATN biomarkers in subjects with cognitive complaints.Methods A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging(18F-florbetapir for A,18F-Florzolotau for T,and 18F-fluorodeoxyglucose[18F-FDG]for N)was enrolled(n=137).Theβ-amyloid(Aβ)status(positive versus negative)and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances.Results Plasma phosphorylated tau 181(p-tau181)level was found to be associated with PET imaging of ATN biomarkers in the entire cohort.Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+and Aβ−subjects.An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+subjects.Additionally,glucose hypometabolism-along with elevated plasma neurofilament light chain level-was related to more severe cognitive impairment in Aβ−subjects.Conclusion Plasma p-tau181,as well as 18F-florbetapir and 18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβstatus in symptomatic stages of AD.18F-Florzolotau and 18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment.Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.
文摘This Bombesin (BBN), a tetradecapeptide analog of human gastrin-releasing peptide (GRP) with a high binding affinity for GRP receptors (GRPR), is over- expressed in early stages of androgen-dependent prostate carcinomas, but not in advanced stages. Therefore, there is a need to develop effective tracers for the accurate and specific detection of this disease. The objective of this study was to evaluate Lys<sup>1</sup>, Lys<sup>3</sup>-DOTA-BBN (1,14) analog with the radiolabeled positron emitter [<sup>68</sup>Ga]-Ga-BBN for receptor imaging with PET, and to determine its biodistribution and radiation dosimetry using whole-body (WB) PET scans in healthy volunteers. The highest uptake was in the pancreas, followed by urinary bladder. The critical organ was pancreas with a mean absorbed dose of 206 ± 0.7, 210 ± 0.7, 120 ± 0.9, 390.23 ± 0.6 μGy/MBq and the effective doses were estimated as 73.2 ± 0.6, 49.8 ± 0.3 μGy/MBq (women and men, respectively).
基金supported by George Mason University and the state of Virginia.
文摘The development of peptide-based,radiometal-labeled PET imaging agents has seen an increase in attention due to the favorable properties the peptide backbone exhibits.These include high selectivity and affinity to proteins and cells directly linked to various types of cancers.In addition,rapid clearance from circulation and low toxicity allow for unique approaches to engineering a viable peptide-based imaging agent.Utilizing peptides as the backbone allows for various modifications to improve metabolic stability,target cell affinity,and image quality and imaging capabilities and reduce toxicity.Select radiolabeled peptides have already been FDA approved,with many more in late-stage trials.This review summarizes the current state of the radiometal-labeled PET peptide imaging field as well as explores methods used by researchers to modify peptides,concluding with a look at the future of peptide-based therapy and diagnostics.
基金supported by the Eisenberg Depression Center Impact Accelerator Grant.
文摘Background With bipolar disorder(BD)having a lifetime prevalence of 4.4%and a significant portion of patients being chronically burdened by symptoms,there has been an increased focus on uncovering new targets for intervention in BD.One area that has shown early promise is the mitochondrial hypothesis.However,at the time of publication no studies have utilized positron emission tomography(PET)imaging to assess mitochondrial function in the setting of BD.Case Presentation Our participant is a 58 year-old male with a past medical history notable for alcohol use disorder and BD(unspecified type)who underwent PET imaging with the mitochondrial complex I PET ligand^(18)F-BCPP-EF.The resulting images demonstrated significant overlap between areas of dysfunction identified with the^(18)F-BCPP-EF PET ligand and prior functional magnetic resonance imaging(MRI)techniques in the setting of BD.That overlap was seen in both affective and cognitive circuits,with mitochondrial dysfunction in the fronto-limbic,ventral affective,and dorsal cognitive circuits showing particularly significant differences.Conclusions Despite mounting evidence implicating mitochondria in BD,this study represents the first PET imaging study to investigate this mechanistic connection.There were key limitations in the form of comorbid alcohol use disorder,limited statistical power inherent to a case study,no sex matched controls,and the absence of a comprehensive psychiatric history.However,even with these limitations in mind,the significant overlap between dysfunction previously demonstrated on functional MRI and this imaging provides compelling preliminary evidence that strengthens the mechanistic link between mitochondrial dysfunction and BD.
基金This study was supported by the National Natural Science Foundation of China(grant numbers:31972644,32272959)the University Synergy Innovation Program of Anhui Province(grant number:GXXT-2019-035)+1 种基金the Jiangsu Provincial Medical Innovation Team(grant number:CXTDA2017024)the leading technology foundation research project of Jiangsu Province(grant number:BK20192005).
文摘Background:The chicken chorioallantoic membrane(CAM)model is a potential alter-native to the mouse model based on the 3R principles.However,its value for deter-mination of the in vivo behaviors of radiolabeled peptides through positron emission tomography(PET)imaging needed investigation.Herein,the chicken CAM tumor models were established,and their feasibility was evaluated for evaluating the imag-ing properties of radiolabeled peptides using a 68Ga-labeled HER2 affibody.Methods:Two human breast cancer cell lines were inoculated into chicken CAM and mice,respectively.The tumor-targeting potential and pharmacokinetic profile of a 68Ga-labeled affibody,68Ga-MZHER,in both tumor models were also determined.Results:The tumor-formation time in chicken CAM model was shorter than that of mouse model.The uptake values of human epithelial growth factor receptor-2(HER2)-positive Bcap37 tumors in chicken CAM and mouse models were 5.36±0.26%ID/g and 5.26±0.43%ID/g at 30 min postinjection of 68Ga-MZHER,respectively.At the same time points,the uptake values of HER2-negative MDA-MB-231 tumors in the chicken CAM models and mouse models were 1.57±0.15%ID/g and 1.67±0.25%ID/g,respectively.Ex vivo biodistribution confirmed that more radioactivity accu-mulated in Bcap37 tumors than in MDA-MD-231 tumors in both CAM and mouse models.Conclusion:In this study,the CAM tumor model was successfully prepared.The chicken CAM model is a novel tool for quickly determining the in vivo properties of radiolabeled peptides targeting biomarkers.It may be beneficial for early monitoring of the therapeutic effect of a new drug through PET imaging with specific peptides.
基金supported by Scientific Research Deanship at University of Ha’il,Saudi Arabia through project number RG-23137.
文摘The segmentation of head and neck(H&N)tumors in dual Positron Emission Tomography/Computed Tomogra-phy(PET/CT)imaging is a critical task in medical imaging,providing essential information for diagnosis,treatment planning,and outcome prediction.Motivated by the need for more accurate and robust segmentation methods,this study addresses key research gaps in the application of deep learning techniques to multimodal medical images.Specifically,it investigates the limitations of existing 2D and 3D models in capturing complex tumor structures and proposes an innovative 2.5D UNet Transformer model as a solution.The primary research questions guiding this study are:(1)How can the integration of convolutional neural networks(CNNs)and transformer networks enhance segmentation accuracy in dual PET/CT imaging?(2)What are the comparative advantages of 2D,2.5D,and 3D model configurations in this context?To answer these questions,we aimed to develop and evaluate advanced deep-learning models that leverage the strengths of both CNNs and transformers.Our proposed methodology involved a comprehensive preprocessing pipeline,including normalization,contrast enhancement,and resampling,followed by segmentation using 2D,2.5D,and 3D UNet Transformer models.The models were trained and tested on three diverse datasets:HeckTor2022,AutoPET2023,and SegRap2023.Performance was assessed using metrics such as Dice Similarity Coefficient,Jaccard Index,Average Surface Distance(ASD),and Relative Absolute Volume Difference(RAVD).The findings demonstrate that the 2.5D UNet Transformer model consistently outperformed the 2D and 3D models across most metrics,achieving the highest Dice and Jaccard values,indicating superior segmentation accuracy.For instance,on the HeckTor2022 dataset,the 2.5D model achieved a Dice score of 81.777 and a Jaccard index of 0.705,surpassing other model configurations.The 3D model showed strong boundary delineation performance but exhibited variability across datasets,while the 2D model,although effective,generally underperformed compared to its 2.5D and 3D counterparts.Compared to related literature,our study confirms the advantages of incorporating additional spatial context,as seen in the improved performance of the 2.5D model.This research fills a significant gap by providing a detailed comparative analysis of different model dimensions and their impact on H&N segmentation accuracy in dual PET/CT imaging.
文摘Bladder tumor is the most common malignant tumor in urinary system and always com- panied with lymph node metastasis. The accurate staging plays a significant role in treatment for bladder tumor and prognostic evaluation, and the distant metastasis predicts worse prognosis. The objective of this study was to assess the clinical significance of 18F-FDG PET/CT imaging in diagnosing bladder tumor metastasis lesions. A retrospective analysis of 60 patients with bladder tumor from October 2008 to May 2010 was done. The patients were stratified based on the imaging technique. Among all 60 cases, besides the primary lesion, 81 suspected lesions were spotted and 73 confirmed as metastasis, including 50 lymph node metastases, 22 distant metastases, and 1 bone metastasis. For PET/CT imaging, its sensitivity was 94.5%, specificity 87.5%, positive predictive value 98.6%, negative predictive value 63.6% and accuracy 93.8% respectively. For CT, its sensitivity was 82.2%, specificity 50%, positive predictive value 93.8%, negative predictive value 23.5% and accuracy 79% respectively. PET/CT im- aging was superior to CT in sensitivity, specificity and accuracy. In conclusion, 18F-FDG PET/CT imaging is more significant in diagnosing bladder tumor metastasis lesions.
基金supported by grants from the Shanghai Municipal Key Clinical Specialty Project(SHSLCZDZK03401)Shanghai Science and Technology Project(19DZ1930700)+1 种基金the Shanghai Science and Technology Committee Program(20DZ2201800)the Three-year Action Plan of Clinical Skills and Innovation of Shanghai Hospital Development Center(SHDC2020CR3079B).
文摘The cause of obstructive jaundice is usually complex which renders its differential diagnosis and lesion localization challenging in clinical practice.Integrated Positron Emission tomography/Magnetic Resonance(PET/MR)offers complementary information from PET and MR in the diagnosis of obstructive jaundice and is becoming widely adopted in clinical setting.While preserving its diagnostic accuracy,it is important to standardize and streamline the clinical scan protocol of PET/MR in evaluating obstructive jaundice.Based on literature review and experience of large number of clinical cases from the author group,this article reports an expert consensus on imaging protocol optimization and case interpretation template standardization.
基金supported by National Natural Science Foundation of China(No.82002241)National Key Research and Development Program of China(No.2020YFA0909000)“Clinic Plus”Outstanding Project(No.2024ZY012)from Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine。
文摘Diabetes and insulinoma represent opposing alterations in pancreatic β-cell mass,with diabetes resulting from irreversible β-cells damage and insulinoma arising from abnormal proliferation.Early diagnosis of both conditions necessitates effectiveβ-cell mass detection.Current detection methods are limited in diagnosing each condition individually or lacking timely and accurate detection.Diabetes is typically identified only after significantβ-cell loss,while insulinoma can evade conventional imaging due to their small size.Positron emission tomography/computed tomography(PET/CT)imaging,combining anatomical and functional data,enhances diagnostic accuracy but faces challenges in specificity.This study employed two RNA aptamers(m12–3773 and 1–717)modified to enhance RNase resistance and conjugated with68Ga to create ^(68)Ga-NOTA-Ap.^(68)Ga-NOTA-Ap was administered to rats with pancreaticβ-cell damage and mice with insulinoma to evaluate its ability to image islets,detect changes in pancreatic β-cell mass(BCM),and identify insulinoma.Modified with methoxy and fluoro,RNA aptamers exhibited enhanced stability and RNases resistance while retaining their dissociation constants(K_(d)).Furthermore,^(68)Ga-NOTA-Ap effectively detected changes of BCM in rats with pancreatic β-cell damage and imaged insulinoma in mice through recognition of abnormalβ-cell proliferation by recognizing clusterin and transmembrane p24 trafficking protein 6(TMED6)on pancreaticβ-cell.The developed ^(68)Ga-NOTA-Ap shows promise for early screening of diabetes and insulinoma due to its high sensitivity,specificity,and non-invasive nature.It has potential clinical applications for monitoring pancreatic β-cell function and diagnosing insulinoma.
基金supported by the Science and Technology Innovation Team Talent Project of Hunan Province(No.2021RC4056)the clinical research foundation of the National Clinical Research Center for Geriatric Diseases(XIANGYA)(No.2020LNJJ01)+1 种基金the Natural Science Foundation of Hunan Province in China(No.2021JJ20084)the Science and Technology Innovation Program of Hunan Province(No.2021RC3020)。
文摘Polyamine metabolism dysregulation is a hallmark of many cancers,offering a promising avenue for early tumor theranostics.This study presents the development of a nuclear probe derived from spermidine(SPM)for dual-purpose tumor PET imaging and internal radiation therapy.The probe,radiolabeled with either[68Ga]Ga for diagnostic applications or[177Lu]Lu for therapeutic use,was synthesized with exceptional purity,stability,and specific activity.Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells,showcasing outstanding tumor localization and target-to-non-target ratio.Mechanistic investigations employing polyamines,non-labeled precursor,and polyamine transport system(PTS)inhibitor,consistently affirmed the probe?s targetability through recognition of the PTS.Notably,while previous reports indicated PTS upregulation in various tumor types for targeted therapy,this study observed no positive signals,highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis.Furthermore,when labeled with[177Lu],the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival.Investigations into biodistribution,excretion,and biosafety in healthy humans laid a robust foundation for clinical translation.This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics,offering promising prospects for clinical implementation.
基金funded by National Natural Science Foundation of China No.62062003Ningxia Natural Science Foundation Project No.2023AAC03293.
文摘The precise detection and segmentation of tumor lesions are very important for lung cancer computer-aided diagnosis.However,in PET/CT(Positron Emission Tomography/Computed Tomography)lung images,the lesion shapes are complex,the edges are blurred,and the sample numbers are unbalanced.To solve these problems,this paper proposes a Multi-branch Cross-scale Interactive Feature fusion Transformer model(MCIF-Transformer Mask RCNN)for PET/CT lung tumor instance segmentation,The main innovative works of this paper are as follows:Firstly,the ResNet-Transformer backbone network is used to extract global feature and local feature in lung images.The pixel dependence relationship is established in local and non-local fields to improve the model perception ability.Secondly,the Cross-scale Interactive Feature Enhancement auxiliary network is designed to provide the shallow features to the deep features,and the cross-scale interactive feature enhancement module(CIFEM)is used to enhance the attention ability of the fine-grained features.Thirdly,the Cross-scale Interactive Feature fusion FPN network(CIF-FPN)is constructed to realize bidirectional interactive fusion between deep features and shallow features,and the low-level features are enhanced in deep semantic features.Finally,4 ablation experiments,3 comparison experiments of detection,3 comparison experiments of segmentation and 6 comparison experiments with two-stage and single-stage instance segmentation networks are done on PET/CT lung medical image datasets.The results showed that APdet,APseg,ARdet and ARseg indexes are improved by 5.5%,5.15%,3.11%and 6.79%compared with Mask RCNN(resnet50).Based on the above research,the precise detection and segmentation of the lesion region are realized in this paper.This method has positive significance for the detection of lung tumors.
基金supported by Scientific research project of Jiangsu Provincial Health Commission(M2021053)Jiangsu Provincial Health Commission Capacity Enhancement Project(ZDXYS202211).
文摘Reactive oxygen species(ROS)are involved in the onset and development of neurodegenerative diseases,such as Alzheimer's disease(AD)and Parkinson's disease(PD).Hydrogen peroxide(H_(2)O_(2)),a key type of ROS,is overexpressed in the early stages of AD and PD and is involved in the disease progression.Assessing H_(2)O_(2) levels in the brain is considered to be a valuable tool for detecting neurodegenerative diseases and exploring their pathogenesis.In this study,we developed two self-immobilizing PET tracers([^(18)F]HYAS and[^(18)F]HYAT)based on a quinone methide(QM)scaffold for non-invasive imaging of H_(2)O_(2) in the brain.Both tracers can respond to H_(2)O_(2) by forming a QM intermediate,which rapidly reacts with nucleophiles.[^(18)F]HYAT,with proper physicochemical properties,is able of crossing the blood-brain barrier.Increased uptake of[^(18)F]HYAT was observed in the brains of mice treated with 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine(MPTP),indicating that[^(18)F]HYAT is a useful tracer for PET imaging of H_(2)O_(2) in the brain.
文摘Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography(PET)for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b,are synthesized.The triflate agent,9a or 9b,is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine,protection of the amine group with di-tert-butyl dicarbonate,alkylation with chlorohydrin,and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 30%and 15%,respectively.
基金supported by pilot funding from the Martinos Center (to Changning Wang, USA)the Cure Alzheimer’s Fund, USA
文摘Although the epigenetic regulatory protein histone deacetylase 6(HDAC6)has been recently implicated in the etiology of Alzheimer’s disease(AD),little is known about the role of HDAC6 in the etiopathogenesis of AD and whether HDAC6 can be a potential therapeutic target for AD.Here,we performed positron emission tomography(PET)imaging in combination with histopathological analysis to better understand the underlying pathomechanisms of HDAC6 in AD.We first developed[^(18)F]PB118 which was demonstrated as a valid HDAC6 radioligand with excellent brain penetration and high specificity to HDAC6.PET studies of[^(18)F]PB118 in 5xFAD mice showed significantly increased radioactivity in the brain compared to WT animals,with more pronounced changes identified in the cortex and hippocampus.The translatability of this radiotracer for AD in a potential human use was supported by additional studies,including similar uptake profiles in non-human primates,an increase of HDAC6 in ADrelated human postmortem hippocampal tissues by Western blotting protein analysis,and our ex vivo histopathological analysis of HDAC6 in postmortem brain tissues of our animals.Collectively,our findings show that HDAC6 may lead to AD by mechanisms that tend to affect brain regions particularly susceptible to AD through an association with amyloid pathology.
基金This work was supported by GE Healthcare,No.12496139131(to DPF and CAB)。
文摘^(11)C-PK11195 is a positron emitter tracer used for Positron Emission Tomography(PET)imaging of innate immune cell activation in studies of neuroinflammatory diseases.For the image quantitative analysis,it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition(plasma intact fraction).Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition.The purpose of this study is to compare 11CPK11195 plasma metabolization rate between healthy controls and multiple sclerosis(MS)patients and evaluate the interference of sex,age,treatment,and disease phenotype in the tracer intact fraction measured in arterial plasma samples.11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients(n=50)and healthy controls(n=23)at 20,45,and 60 minutes after 11C-PK11195 injection.Analyses were also stratified by sex,age,treatment type,and MS phenotype.The results showed no significant differences in the metabolization rate of healthy controls and MS patients,or in the stratified samples.In conclusion,11C-PK11195 metabolization has the same rate in patients with MS and healthy controls,which is not affected by sex,age,treatment,and disease phenotype.Thus,these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition,by using a population metabolization rate average.The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School(approval No.624.065)on April 23,2014.
基金supported by R4012-18,C6021-19EF and GRF 16306919 from the Research Grant Council(RGC)ITS/480/18FP and MHP/033/20+2 种基金from the Innovation and Technology Commission(ITC)of the Hong Kong S.A.R.,Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Projec(HZQB-KCZYB-2020083)the National Natural Science Foundation of China(U1809204)the Talent Program of Zhejiang Province(2021R51004)。
文摘In animal experiments,ischemic stroke is usually induced through middle cerebral artery occlusion(MCAO),and quality assessment of this procedure is crucial.However,an accurate assessment method based on 18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)is still lacking.The difficulty lies in the inconsistent preprocessing pipeline,biased intensity normalization,or unclear spatiotemporal uptake of FDG.Here,we propose an image feature-based protocol to assess the quality of the procedure using a 3D scale-invariant feature transform and support vector machine.This feature-based protocol provides a convenient,accurate,and reliable tool to assess the quality of the MCAO procedure in FDG PET studies.Compared with existing approaches,the proposed protocol is fully quantitative,objective,automatic,and bypasses the intensity normalization step.An online interface was constructed to check images and obtain assessment results.
文摘1-[^18F]Fluoro-l-deoxy-2,5-anhydro-D-mannitol （3, ^18F-FDAM） has been synthesized in 6 steps starting from 2,5-anhydro-D-mannitol （2,5-AM） and evaluated as a new radiotracer for PET imaging of MCF-7 breast tumor. The result of PET imaging study showed that 3 displayed a slightly higher uptake by breast tumor in comparison with the normal breast tissue, implying the possibility of development of PET radiotraeers based on targeting fructose transporters.
