[18F]FDG

[18F] FDG
  • 文章类型: Journal Article
    脑膜瘤的肝转移很少见,特别是当他们作为一个延迟,孤立性转移,这对基于成像的诊断提出了挑战。[18F]FDGPET/CT有助于诊断和治疗后再分类,而生长抑素受体靶向PET在脑膜瘤的诊断中显示出高敏感性和特异性,并且可能潜在地评估治疗方法的可行性,特别是治疗抗性脑膜瘤。
    Hepatic metastases of cranial meningiomas are rare, particularly when they present as a delayed, solitary metastasis, which poses a challenge for imaging-based diagnosis. [18F]FDG PET/CT facilitates diagnosis and posttreatment restaging, whereas somatostatin receptor-targeted PET demonstrates high sensitivity and specificity in the diagnosis of meningiomas and may potentially evaluate the viability of theranostics approaches, particularly for treatment-resistant meningiomas.
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  • 文章类型: Journal Article
    背景:[18F]先前发现使用深度学习人工智能(AI)通过SubtlePET™进行FDGPET去噪在病变和参考器官量化以及病变检测中引起轻微的改变。作为下一步,我们旨在评估其对[18F]FDGPET实体肿瘤治疗反应评估的临床影响,同时在随访期间将“标准PET”与“AI去噪的半持续时间PET”(“AIPET”)进行比较。
    结果:前瞻性纳入110例基线和随访标准数字[18F]FDGPET/CT患者。“标准”EORTC和,如果适用,将基线标准PET1和作为“金标准”的后续标准PET2之间的2位读者的PERCIST反应分类与标准PET1和AIPET2之间的“混合”分类进行比较(第1组;n=64),或介于AIPET1和标准PET2之间(第2组;n=46)。使用具有或不具有AI去噪(简化为“UHD”)的超高清PET的标准化摄取值或EANM研究有限v2(EARL2)兼容值(通过在标准PET中进行高斯滤波并使用相同的AIPET滤波器)建立单独的分类。总的来说,汇集两个研究组,在11/110(10%)患者中,至少有一个EORTCUHD或EARL2或PERCISTUHD或EARL2混合与标准分类不一致,具有369/397(93%)的一致性分类,未加权科恩的kappa=0.86(95%CI:0.78-0.94)。这些改良的混合与标准分类可能影响2%患者的管理.
    结论:尽管比较相似的PET图像对于治疗反应评估更可取,标准[18F]FDGPET和AI去噪半程PET之间的比较是可行的,并且临床上似乎令人满意.
    BACKGROUND: [18F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs\' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [18F]FDG PET solid tumour treatment response assessments, while comparing \"standard PET\" to \"AI denoised half-duration PET\" (\"AI PET\") during follow-up.
    RESULTS: 110 patients referred for baseline and follow-up standard digital [18F]FDG PET/CT were prospectively included. \"Standard\" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a \"gold standard\" were compared to \"mixed\" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to \"UHD\") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTCUHD or EARL2 or PERCISTUHD or EARL2 mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen\'s kappa = 0.86 (95% CI: 0.78-0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients.
    CONCLUSIONS: Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [18F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory.
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  • 文章类型: Journal Article
    目的:伴有炎症的心肌梗死(MI)是导致进行性组织损伤的最常见心脏病之一。评估MI后组织活力的可靠成像标记将有助于确定任何干预的风险和益处。在这项研究中,我们研究了一种新的线粒体靶向显像剂,18F标记的2'-脱氧-2'-18F-氟-9-β-d-阿拉伯呋喃基鸟嘌呤([18F]F-AraG),一种正电子发射断层扫描(PET)试剂开发的成像激活的T细胞,适用于心脏成像和MI后测试心肌活力。
    方法:为了测试心肌[18F]-F-AraG信号是否来自心肌细胞或免疫浸润,我们比较了野生型(WT)小鼠和T细胞缺陷型Rag1基因敲除(Rag1KO)小鼠的心脏信号.我们通过比较用纯化饮食喂养的小鼠和用补充核苷酸的纯化饮食喂养的小鼠之间的[18F]F-AraG信号,评估了饮食核苷酸对正常心脏中心肌[18F]F-AraG摄取的影响。在MI前后,通过用[18F]F-AraG和2-脱氧-2[18F]氟-D-葡萄糖([18F]FDG)对大鼠进行成像,在啮齿动物模型中研究了心肌活力。所有PET信号以每cc的注射剂量百分比(%ID/cc)定量。我们还通过H&E分析探索了[18F]FDG信号变异性和潜在的T细胞浸润到受影响的心肌中的纤维化区域。
    结果:RaglKO和WT小鼠的%ID/cc差异不显著(p=ns),表明心肌中的[18F]F-AraG信号主要来自心肌细胞。在用纯化饮食和补充核苷酸的纯化饮食喂养的小鼠中[18F]F-AraG信号之间没有观察到心肌摄取的差异(p=ns)。[18F]FDG信号在不同时间点显示更宽的变异性。在受影响的MI区域中观察到显著的[18F]F-AraG信号。在H&E分析中纤维化区域有T细胞,但它们并不构成主要的渗透。
    结论:我们的初步临床前数据表明[18F]F-AraG在心肌细胞中积累,表明它可能适用于心脏成像和评估MI后的心肌活力。
    OBJECTIVE: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2\'-deoxy-2\'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI.
    METHODS: To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis.
    RESULTS: The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates.
    CONCLUSIONS: Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.
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  • 文章类型: Journal Article
    [18F]氟-2-脱氧-d-葡萄糖PET/计算机断层扫描已在淋巴瘤患者的管理中实施,提供实时的淋巴瘤代谢信息与更准确的分期承诺,治疗反应评估,预测,早期发现疾病复发。淋巴增生性疾病的临床管理最近,从最初的化疗药物迅速发展到免疫疗法的使用,有针对性的特工,以及嵌合抗原受体T细胞疗法的应用。这些新系统和成像协议的实施以及新的示踪剂的开发创造了,在淋巴增生性疾病领域,机遇和挑战都将在这篇全面的文献综述中详细介绍。
    [18F]fluoro-2-deoxy-d-glucose PET/computed tomography has been implemented in the management of patients with lymphoma, offering real-time metabolic information on lymphoma with the promise of more accurate staging, treatment response assessment, prognostication, and early detection of disease recurrence. The clinical management of lymphoproliferative disease has recently, rapidly evolved from initial chemotherapeutic to the use of immunotherapy, targeted agents, and to the use of chimeric antigen receptor T-cell therapies. The implementation of these new systems and imaging protocols together with new tracer development creates, in the field of lymphoproliferative disease, both opportunities and challenges that will be detailed in this comprehensive literature review.
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  • 文章类型: Journal Article
    背景:葡萄膜黑色素瘤(UM)是成人最常见的原发性眼内肿瘤,早期发现对于改善这种疾病的临床结局至关重要。在这项研究中,评估了[18F]AlF-NOTA-PRGD2(一种研究药品)正电子发射断层扫描(PET)成像在UM异种移植物和UM患者中的诊断效果.细胞的摄取,在92-1UM细胞系中评估了[18F]AlF-NOTA-PRGD2的细胞结合能力和体外稳定性。在92-1UM异种移植物中进行[18F]AlF-NOTA-PRGD2的MicroPET成像和生物分布研究。然后,进一步招募UM患者以评估[18F]AlF-NOTA-PRGD2PET成像的诊断有效性(批准号NCT02441972inclinicaltrials.gov).此外,在UM异种移植物和UM患者中进行了[18F]AlF-NOTA-PRGD2和18F标记的氟脱氧葡萄糖([18F]FDG)PET成像的比较。
    结果:体外数据显示[18F]AlF-NOTA-PRGD2具有高细胞摄取,92-1UM细胞系的细胞结合能力和体外稳定性。体内数据表明,在注射后60分钟,在皮下和眼部原代UM异种移植物模型中,用[18F]AlF-NOTA-PRGD2示踪剂清楚地观察到92-1UM肿瘤。示踪剂在这两个组织部位的肿瘤摄取率分别为2.55±0.44%ID/g和1.73±0.15%ID/g,在动物模型构建后7天。临床数据显示,注射后60分钟,[18F]AlF-NOTA-PRGD2示踪剂清楚地显示了UM患者的肿瘤。此外,与[18F]FDG示踪剂相比,[18F]AlF-NOTA-PRGD2示踪剂对UM异种移植物和UM患者的PET成像显示出更高的敏感性和特异性。
    结论:与[18F]FDGPET成像相比,[18F]AlF-NOTA-PRGD2PET成像可能是诊断原发性UM的更优选方法。此外,由于高的肿瘤背景比,[18F]AlF-NOTA-PRGD2PET显像似乎也适用于诊断有肝转移的UM患者。
    背景:ClinicalTrials.gov:NCT02441972,2012年1月1日注册,https://clinicaltrials.gov/study/NCT02441972。
    BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [18F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [18F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [18F]AlF-NOTA-PRGD2 and 18F-labelled fluorodeoxyglucose ([18F]FDG) PET imaging in UM xenografts and UM patients were conducted.
    RESULTS: The in vitro data showed that [18F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [18F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [18F]FDG tracer.
    CONCLUSIONS: [18F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [18F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [18F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis.
    BACKGROUND: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .
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  • 文章类型: Journal Article
    联合[18F]FDGPET-心脏MRI成像(PET/CMR)是评估急性心肌梗死(AMI)患者心肌活力和心脏功能的有用工具。这里,我们评估了PET/CMR在猪闭胸再灌注AMI(rAMI)模型中的预后价值.通过PET/CMR成像的晚期钆增强在大多数动物的rAMI后3天显示出梗死部位的示踪剂摄取缺陷(组Match,n=28)。梗死区的[18F]FDG摄取增加(代谢/收缩性不匹配),远端存活心肌示踪剂摄取减少(Mismatch组,n=12)在rAMI后3天,在梗死面积较大且左心室射血分数(LVEF)较差的动物中观察到(34±8.7vs42.0±5.2%),在1个月的随访中,LVEF也较低(35.8±9.5vs43.0±6.3%)。通过梗死心肌和边界区的批量和单核RNA测序进行转录组分析(每组n=3,和3个假手术对照)显示出强烈的炎症反应,在Mismatch动物的梗塞和边界区域中单核细胞和巨噬细胞浸润。我们的数据表明,在rAMI的亚急性期,联合PET/MRI与随后的心功能损害具有很高的预后相关性,并强调了rAMI后初始阶段先天免疫系统过度激活的不利影响。
    Combined [18F]FDG PET-cardiac MRI imaging (PET/CMR) is a useful tool to assess myocardial viability and cardiac function in patients with acute myocardial infarction (AMI). Here, we evaluated the prognostic value of PET/CMR in a porcine closed-chest reperfused AMI (rAMI) model. Late gadolinium enhancement by PET/CMR imaging displayed tracer uptake defect at the infarction site by 3 days after the rAMI in the majority of the animals (group Match, n = 28). Increased [18F]FDG uptake at the infarcted area (metabolism/contractility mismatch) with reduced tracer uptake in the remote viable myocardium (group Mismatch, n = 12) 3 days after rAMI was observed in the animals with larger infarct size and worse left ventricular ejection fraction (LVEF) (34 ± 8.7 vs 42.0 ± 5.2%), with lower LVEF also at the 1-month follow-up (35.8 ± 9.5 vs 43.0 ± 6.3%). Transcriptome analyses by bulk and single-nuclei RNA sequencing of the infarcted myocardium and border zones (n = 3 of each group, and 3 sham-operated controls) revealed a strong inflammatory response with infiltration of monocytes and macrophages in the infarcted and border areas in Mismatch animals. Our data indicate a high prognostic relevance of combined PET/MRI in the subacute phase of rAMI for subsequent impairment of heart function and underline the adverse effects of an excessive activation of the innate immune system in the initial phase after rAMI.
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  • 文章类型: Journal Article
    CAR-T细胞疗法,也称为嵌合抗原受体T细胞疗法,是免疫治疗非霍奇金淋巴瘤(NHL)领域的一种新方法。在接受CAR-T细胞治疗的患者中,氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描([18F]FDGPET/CT)在追踪治疗反应和评估免疫治疗的整体疗效方面发挥着关键作用。这项研究的目的是对旨在通过[18F]FDGPET/CT评估和预测接受CAR-T细胞治疗的NHL患者毒性的研究文献进行系统综述。两名研究人员询问了PubMed/MEDLINE和Cochrane中央对照试验注册(CENTRAL)数据库,以寻求涉及在接受CAR-T细胞治疗的淋巴瘤患者中使用[18F]FDGPET/CT的研究。全面的计算机文献检索允许纳入11项研究。通过使用第2版“诊断准确性研究质量评估”工具(QUADAS-2),系统评价中纳入的研究的偏倚风险评分为低。目前的文献强调[18F]FDGPET/CT在评估和预测接受CAR-T细胞治疗的NHL患者的毒性中的作用。强调CAR-T细胞疗法研究的演变性质。需要更多的研究来增加文献中收集的证据。
    CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin\'s lymphoma (NHL). In patients receiving CAR-T-cell therapy, fluorodeoxyglucose Positron Emission Tomography/Computer Tomography ([18F]FDG PET/CT) plays a critical role in tracking treatment response and evaluating the immunotherapy\'s overall efficacy. The aim of this study is to provide a systematic review of the literature on the studies aiming to assess and predict toxicity by means of [18F]FDG PET/CT in patients with NHL receiving CAR-T-cell therapy. PubMed/MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were interrogated by two investigators to seek studies involving the use of [18F]FDG PET/CT in patients with lymphoma undergoing CAR-T-cell therapy. The comprehensive computer literature search allowed 11 studies to be included. The risk of bias for the studies included in the systematic review was scored as low by using version 2 of the \"Quality Assessment of Diagnostic Accuracy Studies\" tool (QUADAS-2). The current literature emphasizes the role of [18F]FDG PET/CT in assessing and predicting toxicity in patients with NHL receiving CAR-T-cell therapy, highlighting the evolving nature of research in CAR-T-cell therapy. Additional studies are warranted to increase the collected evidence in the literature.
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  • 文章类型: Journal Article
    目的:比较全身[68Ga]Ga-FAPI-04和[18F]FDGPET成像在Krukenberg肿瘤(KTs)检测中的表现,胃印戒细胞癌(GSRCC)的原发部位和卵巢外转移,并评估[68Ga]Ga-FAPI-04PET/MR成像策略的价值及其对GSRCCKTs管理的潜在影响。
    方法:来自GSRCC的12例患者,其中23例KT,回顾性分析同时接受[68Ga]Ga-FAPI-04骨盆PET/MR和全身[68Ga]Ga-FAPI-04和[18F]FDGPET成像的患者。通过使用Wilcoxon符号秩检验或配对t检验比较[68Ga]Ga-FAPI-04和[18F]FDG摄取。McNemar检验用于比较两种模式之间的病变可检测性。双尾P<0.05被认为具有统计学意义。免疫组织化学染色用于分析成纤维细胞活化蛋白(FAP)在KT中的表达。
    结果:共评估了12例来自GSRCC的23KT患者(8例同步,4例异时)。[68Ga]Ga-FAPI-04在检测GSRCC的主要部位方面优于[18F]FDGPET(100%[11/11]与18.2%[2/11],p=0.002),受累淋巴结(90.9%[10/11]vs.54.5%[6/11],p=0.046)和腹膜转移(100%[12/12]vs.41.7%[5/12],p=0.008),具有较高的SUVmax和TBR(所有p<0.005)。两种示踪剂在鉴定KTs方面的价值有限,在[68Ga]Ga-FAPI-04PET上具有100%的假阴性率,在[18F]FDGPET上具有8.7%的低检出率。Fap免疫组织化学显示肿瘤印戒细胞和卵巢间质中FAP阴性或轻度表达。[68Ga]Ga-FAPI-04PET/MR成像策略大大提高了Krukenberg肿瘤的检出率(87%,20/23).加入弥散加权成像(DWI)后,检出率进一步提高(87.5%vs.100%,p=0.083)。[68Ga]Ga-FAPI-04PET/MR成像策略在12名患者中升级了TNM分期或改变了治疗管理。
    结论:[68Ga]Ga-FAPI-04PET在检测GSRCC的原发部位和大多数卵巢外转移方面优于[18F]FDGPET,但是两种示踪剂在识别Krukenberg肿瘤方面的价值有限。应应用骨盆MRI来补偿[68Ga]Ga-FAPI-04PET成像的局限性,以识别Krukenberg肿瘤。[68Ga]Ga-FAPI-04PET/MR成像策略有可能影响患有KTs的GSRCC患者的治疗决策。
    OBJECTIVE: To compare performance of whole-body [68Ga]Ga-FAPI-04 and [18F]FDG PET imaging in the detection of Krukenberg tumors (KTs), primary site and extra-ovarian metastases of gastric signet-ring-cell carcinoma (GSRCC), and evaluate the value of [68Ga]Ga-FAPI-04 PET/MR imaging strategy and its potential impact on the management of KTs from GSRCC.
    METHODS: Twelve patients with twenty-three KTs from GSRCC, who underwent both [68Ga]Ga-FAPI-04 pelvic PET/MR and whole-body [68Ga]Ga-FAPI-04 and [18F]FDG PET imaging were retrospectively analyzed. [68Ga]Ga-FAPI-04 and [18F]FDG uptakes were compared by using Wilcoxon signed-rank test or paired t test. McNemar\'s test was used to compare lesion detectability between two modalities. Two-tailed P<0.05 was considered statistically significant. Immunohistochemistry staining was utilized to analyze the fibroblast activation protein (FAP) expression in KTs.
    RESULTS: A total of 12 patients with 23 KTs from GSRCC (8 synchronous and 4 metachronous) were evaluated. [68Ga]Ga-FAPI-04 was superior to [18F]FDG PET in detecting primary sites of GSRCC (100% [11/11] vs. 18.2% [2/11], p = 0.002), involved lymph nodes (90.9% [10/11] vs. 54.5% [6/11], p = 0.046) and peritoneal metastases (100% [12/12] vs. 41.7% [5/12], p = 0.008), with higher SUVmax and TBR (all p < 0.005). Both tracers had limited value in identifying KTs, with 100% false negative rate on [68Ga]Ga-FAPI-04 PET and a low detection rate of 8.7% on [18F]FDG PET. Fap immunohistochemistry showed negative or slight FAP expression in neoplastic signet ring cells and ovarian stroma. [68Ga]Ga-FAPI-04 PET/MR imaging strategy greatly improved the detection rate of Krukenberg tumors (87%, 20/23). After adding diffusion-weighted imaging (DWI), the detection rate was further improved (87.5% vs. 100%, p = 0.083). [68Ga]Ga-FAPI-04 PET/MR imaging strategy either upgraded TNM staging or changed treatment management in twelve patients.
    CONCLUSIONS: [68Ga]Ga-FAPI-04 PET outperformed [18F]FDG PET in detecting primary site and most extra-ovarian metastases of GSRCC, but both tracers had limited value in identifying Krukenberg tumors. Pelvis MRI should be applied to compensate the limitation of [68Ga]Ga-FAPI-04 PET imaging to identify Krukenberg tumours. The [68Ga]Ga-FAPI-04 PET/MR imaging strategy has the potential to impact treatment decisions for GSRCC patients with KTs.
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  • 文章类型: Preprint
    目的:心肌梗死(MI)并随后发生炎症是导致进行性组织损伤的最常见心脏病之一。评估MI后组织活力的可靠成像标记将有助于确定任何干预的风险和益处。在这项研究中,我们研究了一种新的线粒体靶向显像剂,18F标记的2'-脱氧-2'-18F-氟-9-β-d-阿拉伯呋喃基鸟嘌呤([18F]F-AraG),一种正电子发射断层扫描(PET)试剂开发的成像激活的T细胞,适用于心脏成像和MI后测试心肌活力。程序:为了测试心肌[18F]-F-AraG信号是否来自心肌细胞或免疫浸润,我们比较了野生型(WT)小鼠和T细胞缺陷型Rag1基因敲除(Rag1KO)小鼠的心脏信号.我们通过比较用纯化饮食喂养的小鼠和用补充核苷酸的纯化饮食喂养的小鼠之间的[18F]F-AraG信号,评估了饮食核苷酸对正常心脏中心肌[18F]F-AraG摄取的影响。在MI前后,通过用[18F]F-AraG和2-脱氧-2[18F]氟-D-葡萄糖([18F]FDG)对大鼠进行成像,在啮齿动物模型中研究了心肌活力。所有PET信号以每cc的注射剂量百分比(%ID/cc)定量。我们还通过H&E分析探索了[18F]FDG信号变异性和潜在的T细胞浸润到受影响心肌的纤维化区域。结果:Rag1KO和WT小鼠的%ID/cc差异不显著(p=ns),表明心肌中的[18F]F-AraG信号主要来自心肌细胞。在用纯化饮食和补充核苷酸的纯化饮食喂养的小鼠中[18F]F-AraG信号之间没有观察到心肌摄取的差异(p=ns)。[18F]FDG信号在不同时间点显示出更宽的变异性。在受影响的MI区域中观察到显著的[18F]F-AraG信号。在H&E分析中纤维化区域有T细胞,但它们并不构成主要的渗透。结论:我们的初步临床前数据表明[18F]F-AraG在心肌细胞中积累,表明它可能适用于心脏成像和评估MI后的心肌活力。
    UNASSIGNED: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2\'-deoxy-2\'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI.
    UNASSIGNED: To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis.
    UNASSIGNED: The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates.
    UNASSIGNED: Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.
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  • 文章类型: Journal Article
    饮食引起的体重增加是世界范围内日益增长的健康问题。通常伴有改变系统功能的低度代谢炎症,饮食诱导的改变也可能导致神经退行性疾病的进展。本研究旨在非侵入性研究饮食诱导的阿尔茨海默病APPPS1小鼠模型大脑中的代谢和炎症效应。[18F]FDG,[18F]FTHA,和[18F]GE-180用于野生型和APPPS1小鼠的体内PET成像。大脑中的离体流式细胞术和组织学补充了体内发现。肝脏中的1H-磁共振波谱,使用血浆代谢组学和流式细胞术对白色脂肪组织进行分析,以确认外周的代谢条件。我们发现西方饮食消费后葡萄糖和脂肪酸代谢中断,APPPS1小鼠大脑中神经胶质依赖性神经炎症只有很小的区域变化。进一步的离体研究显示,西方饮食喂养小鼠的大脑中涉及细胞毒性T细胞,并且血浆代谢组被破坏。1H磁共振波谱和免疫学结果显示肝脏和脂肪组织中饮食依赖性炎症样失衡。我们的多模式成像研究强调了脑-肝-脂肪轴和适应性免疫系统在阿尔茨海默病淀粉样蛋白模型中脑稳态破坏中的作用。
    Diet-induced increase in body weight is a growing health concern worldwide. Often accompanied by a low-grade metabolic inflammation that changes systemic functions, diet-induced alterations may contribute to neurodegenerative disorder progression as well. This study aims to non-invasively investigate diet-induced metabolic and inflammatory effects in the brain of an APPPS1 mouse model of Alzheimer\'s disease. [18F]FDG, [18F]FTHA, and [18F]GE-180 were used for in vivo PET imaging in wild-type and APPPS1 mice. Ex vivo flow cytometry and histology in brains complemented the in vivo findings. 1H- magnetic resonance spectroscopy in the liver, plasma metabolomics and flow cytometry of the white adipose tissue were used to confirm metaflammatory condition in the periphery. We found disrupted glucose and fatty acid metabolism after Western diet consumption, with only small regional changes in glial-dependent neuroinflammation in the brains of APPPS1 mice. Further ex vivo investigations revealed cytotoxic T cell involvement in the brains of Western diet-fed mice and a disrupted plasma metabolome. 1H-magentic resonance spectroscopy and immunological results revealed diet-dependent inflammatory-like misbalance in livers and fatty tissue. Our multimodal imaging study highlights the role of the brain-liver-fat axis and the adaptive immune system in the disruption of brain homeostasis in amyloid models of Alzheimer\'s disease.
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