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First Total-Body Kinetics Study of 18F-Flurpiridaz in Healthy Volunteers at Rest and Feasibility of Simplified Quantitative Strategies. 18f -氟吡达在健康志愿者休息时的首次全身动力学研究及简化定量策略的可行性。
Pub Date : 2026-04-02 DOI: 10.2967/jnumed.125.270997
Hao Song,Zhenyu Xiang,Yihan Wang,Jingxu Zhao,Yongpeng Wen,Zhixing Qin,Jia Gao,Zhifang Wu,Ping Wu,Sijin Li
The multiorgan kinetic profile of 18F-flurpiridaz targeting mitochondrial complex I remains inadequately characterized. We aim to characterize preliminary total-body pharmacokinetics of 18F-flurpiridaz in healthy volunteers and evaluate shortened acquisition protocols for clinical translation. Methods: Twelve healthy volunteers were imaged with 18F-flurpiridaz during a 60-min dynamic total-body PET/CT scan on the uEXPLORER scanner at rest. Time-activity curves were derived from volumes of interest generated by an automated CT-based segmentation method applied to motion-corrected dynamic PET images, with manual delineation of the descending aorta, kidney, and breasts. The descending aorta served as the input function for most organs, whereas the pulmonary artery was used for the lungs. The 2-tissue irreversible (2T3K) and 2-tissue reversible (2T4K) compartment models incorporating blood volume and time-delay correction were compared using the Akaike information criterion (AIC). Simplified metrics of distribution volume (V T) from a Logan plot and SUVmean from truncated scans (10, 30, and 60 min) were correlated with the reference 60-min 2T4K V T Results: Four distinct kinetic patterns were observed across different organs. At 60 min, the 2T4K model demonstrated superior fitting performance (lower AIC) in 15 of 18 targeted regions. The 2T3K model exhibited lower AIC in the heart, brain, and kidneys at 10 min. In the thyroid and spinal cord, the optimal model shifted from the 2T3K model at 60 min to the 2T4K model at 10 min. Logan V T from 30-min (r = 0.974) and 60-min (r = 0.979) scans strongly correlated with reference V T Notably, SUVmean around 10-min postinjection also showed strong correlation with reference V T (r = 0.834-0.909), only slightly lower than that observed in the optimal 25-30-min window (r = 0.922; all P < 0.0001). Conclusion: This total-body kinetic atlas of 18F-flurpiridaz supports the use of the 2T4K model for multiorgan quantification, time-dependent model preference, and the feasibility of ultrashort imaging strategies for clinical mitochondrial complex I assessment, establishing a foundation for future applications in oncology (e.g., metabolism evaluation), neurology (e.g., mitochondrial mapping), and integrated cardio-oncology diagnostics.
靶向线粒体复合体I的18f -氟吡达兹的多器官动力学特征仍未充分表征。我们的目的是表征18f -氟吡达兹在健康志愿者体内的初步全身药代动力学,并评估用于临床翻译的缩短获取方案。方法:12名健康志愿者在休息时在uEXPLORER扫描仪上进行60分钟动态全身PET/CT扫描,并使用18f -氟吡达进行成像。时间-活动曲线由基于自动ct的分割方法生成的兴趣体积导出,该分割方法应用于运动校正的动态PET图像,并手动描绘降主动脉,肾脏和乳房。降主动脉是大多数器官的输入功能,而肺动脉是肺的输入功能。采用赤池信息准则(Akaike information criterion, AIC)比较2组织不可逆室室模型(2T3K)和2组织可逆室室模型(2T4K)的血容量和时间延迟校正。Logan图的简化分布体积(V T)和截断扫描(10,30和60分钟)的SUVmean与参考60分钟2T4K V T相关。结果:在不同器官中观察到四种不同的动力学模式。在60分钟时,2T4K模型在18个目标区域中的15个区域显示出优越的拟合性能(较低的AIC)。2T3K模型在10 min时心脏、脑和肾脏的AIC均较低。甲状腺和脊髓的最佳模型从60 min时的2T3K模型转变为10 min时的2T4K模型。注射后30分钟(r = 0.974)和60分钟(r = 0.979)扫描的Logan V T与参考V T呈强相关,注射后10分钟左右的SUVmean也与参考V T呈强相关(r = 0.834-0.909),仅略低于最佳25-30分钟窗口(r = 0.922,均P < 0.0001)。结论:该18F-flurpiridaz的全身动力学图谱支持2T4K模型用于多器官定量、时间依赖模型偏好以及超短成像策略用于临床线粒体复合物I评估的可行性,为未来在肿瘤学(如代谢评估)、神经学(如线粒体制图)和心血管肿瘤综合诊断中的应用奠定了基础。
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引用次数: 0
Dosimetry Analysis of 177Lu-PSMA-I&T in Patients with Low-Volume Oligometastatic Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the LUNAR Trial. 177Lu-PSMA-I&T在低体积少转移性激素敏感前列腺癌患者中的剂量学分析:LUNAR试验的二次分析
Pub Date : 2026-04-02 DOI: 10.2967/jnumed.125.271467
Zachary Ells,Catherine Meyer,Koichiro Kimura,Holly Wilhalme,Minsong Cao,Vinicius B Ludwig,Lena M Unterrainer,David Sennung,Rejah Nabong,Carol Felix,Luca F Valle,Anthony Daley,Johannes Czernin,Magnus Dahlbom,Amar U Kishan,Jeremie Calais
The phase 2 LUNAR trial randomized (1:1) patients with oligorecurrent hormone-sensitive prostate cancer to neoadjuvant [177Lu]Lu-PSMA-I&T (2 cycles, 6.8 GBq) followed by stereotactic body radiotherapy (SBRT) versus SBRT alone. [177Lu]Lu-PSMA-I&T before SBRT was well tolerated and significantly improved PSMA PET/CT-based progression-free survival compared with SBRT alone. Here, we report the estimated absorbed doses (AD) of [177Lu]Lu-PSMA-I&T to organs at risk and lesions. Methods: This analysis was conducted on all 45 patients randomized to the investigational arm. Quantitative SPECT/CT images were acquired at 4, 24, and 72-96 h postinjection of cycle 1. Kidneys, salivary and lacrimal glands, and liver were delineated with deep learning-assisted segmentation, whereas lumbar vertebrae were manually segmented as a surrogate for bone marrow. Planned target volumes were transferred from the SBRT plans to the SPECT/CT series. Registration between time points was manually verified for each segmentation. ADs were estimated using a multiple-time-point voxel-based schema. Time-activity data were fit using a monoexponential function. Partial-volume effects were corrected using volume-specific phantom-based recovery coefficients. Results: In the 45 patients included, the median prostate-specific antigen was 1.10 ng/mL (range, 0.16-14.70 ng/mL). In total, 123 lesions total were identified, with a median per patient of 2 (range, 1-9). Median whole-body total tumor volume was 14.5 cm3 (range, 1.9-145.9 cm3). Median SUVmax on baseline PSMA PET/CT and 24-h SPECT/CT was 3.49 (range, 0.59-45.30) and 0.72 (range, 0.02-34.24), respectively. The AD to the kidneys, parotids, submandibulars, lacrimals, liver, and bone marrow were 0.35 ± 0.10, 0.20 ± 0.10, 0.24 ± 0.10, 0.70 ± 0.49, 0.03 ± 0.01, and 0.005 ± 0.002 Gy/GBq, respectively. The mean dose to bone (n = 38), lymph node (n = 82), and soft tissue (n = 3) lesions were 0.19 ± 0.42, 0.46 ± 0.81, and 0.30 ± 0.38 Gy/GBq, respectively. Conclusion: The ADs from [177Lu]Lu-PSMA-I&T to organs at risk were consistent with prior reports, supporting the safety in patients with oligorecurrent hormone-sensitive prostate cancer. There was substantial heterogeneity in lesion AD estimates on both inter- and intrapatient levels. Because of the limited spatial resolution of SPECT, partial-volume effects can underestimate the AD in small volumes. Nevertheless, 2 neoadjuvant cycles of [177Lu]Lu-PSMA-I&T before SBRT prolonged progression-free survival, consistent with effective treatment of occult disease beyond imaging detectability.
LUNAR 2期试验将低复发激素敏感性前列腺癌患者随机(1:1)分配至新辅助[177Lu]Lu-PSMA-I&T(2个周期,6.8 GBq),然后进行立体定向体放疗(SBRT)和单独SBRT。[177Lu]与单独SBRT相比,SBRT前的Lu-PSMA-I&T耐受性良好,可显著提高PSMA PET/ ct为基础的无进展生存期。在这里,我们报告了[177Lu]Lu-PSMA-I&T对危险器官和病变的估计吸收剂量(AD)。方法:该分析在随机分配到研究组的所有45例患者中进行。在第1周期注射后4、24和72-96 h获得定量SPECT/CT图像。肾脏、唾液腺、泪腺和肝脏用深度学习辅助分割,腰椎则用人工分割代替骨髓。计划的目标体积从SBRT计划转移到SPECT/CT系列。时间点之间的注册是手动验证每个分割。使用基于多时间点体素的模式估计ad。时间-活动数据采用单指数函数拟合。部分体积效应使用体积特定的基于幽灵的恢复系数进行校正。结果:纳入的45例患者中位前列腺特异性抗原为1.10 ng/mL(范围0.16 ~ 14.70 ng/mL)。共发现123个病变,每位患者中位数为2个(范围1-9)。肿瘤全身总体积中位数为14.5 cm3(范围1.9-145.9 cm3)。基线PSMA PET/CT和24小时SPECT/CT的中位SUVmax分别为3.49(范围0.59-45.30)和0.72(范围0.02-34.24)。对肾脏、腮腺、下颌骨、泪腺、肝脏和骨髓的AD分别为0.35±0.10、0.20±0.10、0.24±0.10、0.70±0.49、0.03±0.01和0.005±0.002 Gy/GBq。骨(n = 38)、淋巴结(n = 82)和软组织(n = 3)病变的平均剂量分别为0.19±0.42、0.46±0.81和0.30±0.38 Gy/GBq。结论:[177Lu]Lu-PSMA-I&T对危险器官的影响与既往报道一致,支持低复发性激素敏感性前列腺癌患者的安全性。在患者间和患者内水平上,病变AD的估计存在很大的异质性。由于SPECT的空间分辨率有限,局部体积效应会低估小体积的AD。然而,在SBRT前2个新辅助周期的[177Lu]Lu-PSMA-I&T延长了无进展生存期,与影像检测不到的隐匿性疾病的有效治疗一致。
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引用次数: 0
Whole-Body PET and the Brain-Heart Axis: Toward Sex- and Gender-Sensitive Neurocardiovascular Imaging. 全身PET和脑-心轴:迈向性别和性别敏感的神经心血管成像。
Pub Date : 2026-04-02 DOI: 10.2967/jnumed.126.272293
Federico Caobelli
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引用次数: 0
Longitudinal Evaluation of 18F-MK-6240 Along the Alzheimer Disease Continuum. 18F-MK-6240在阿尔茨海默病连续体中的纵向评价
Pub Date : 2026-04-02 DOI: 10.2967/jnumed.125.271127
Anna O Giarratana,Erin Jonaitis,Robert J Przybelski,Karly Cody,Tobey J Betthauser,Robert Cadman,Sara Frost Alberson,Bradley T Christian,Sterling C Johnson
Understanding the rate of tau accumulation is critical for staging Alzheimer disease (AD), monitoring its progression, and informing clinical trial design. Although PET imaging with 18F-MK-6240, also known as florquinitau, can track tau pathology, longitudinal data remain limited. We evaluated longitudinal tau changes using 18F-MK-6240 PET across cognitive stages and analyzed regional rates of change with the goal of informing future clinical trial outcome measures. Methods: In this observational study, 27 participants with varying cognitive statuses (cognitively unimpaired [CU], mild cognitive impairment [MCI], and AD) underwent 18F-MK-6240 PET at baseline and at 6, 12, and 24 mo (or at 18 and 30 mo during the COVID-19 pandemic). Amyloid positivity at baseline was determined with 11C-labeled Pittsburgh compound B PET. Tau PET data were analyzed as SUV ratios (SUVRs) in regions of interest (ROIs) corresponding to Braak staging as well as the inferior temporal gyrus and 2 composite ROIs (metatemporal composite [MTC]) and an early tau composite. Annualized SUVR changes were compared across groups and correlated with cognitive scores (Mini-Mental State Examination, Clinical Dementia Rating Scale, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale) using the Kruskal-Wallis test. Correlations between the change in SUVR and cognitive outcomes were estimated using Spearman ρ. Results: Baseline 18F-MK-6240 PET showed a minimal signal in CU participants, localized signal to the medial temporal lobe in participants with MCI, and a signal spanning the inferolateral temporal lobe and extending posteriorly along the ventral cortex in participants with AD. Longitudinal analysis showed that the annualized percent change in tau deposition in the MTC was 0.17% ± 4.16, 5.77% ± 2.97, and 4.31% ± 5.84 in the CU, MCI, and AD groups, respectively (P = 0.075). The change in tau deposition was 0.00 ± 0.05, 0.10 ± 0.07, and 0.12 ± 0.16 in the CU, MCI, and AD groups, respectively (P = 0.039). Tau accumulation correlated with a decline on the Alzheimer Disease Assessment Scale-Cognitive Subscale (ρ = 0.43, P < 0.05). Conclusion: 18F-MK-6240 PET tracked tau accumulation over time and provided preliminary evidence that these changes correlate with cognitive decline, supporting its utility for longitudinal AD studies and trial design, with MTC emerging as a promising ROI for clinical trials.
了解tau蛋白积累的速度对于阿尔茨海默病(AD)的分期、监测其进展以及为临床试验设计提供信息至关重要。尽管使用18F-MK-6240(也称为florquinitau)进行PET成像可以追踪tau蛋白病理,但纵向数据仍然有限。我们使用18F-MK-6240 PET评估了认知阶段的纵向tau变化,并分析了区域变化率,目的是为未来的临床试验结果测量提供信息。方法:在这项观察性研究中,27名具有不同认知状态(认知未受损[CU]、轻度认知障碍[MCI]和AD)的参与者在基线和6、12和24个月(或在COVID-19大流行期间的18和30个月)接受了18F-MK-6240 PET检查。用11c标记的匹兹堡化合物B PET测定基线时淀粉样蛋白阳性。Tau PET数据被分析为Braak分期和下颞回对应的感兴趣区域(roi)的SUV比率(SUVRs),以及2个复合roi (metatemporal composite [MTC])和一个早期Tau复合物。使用Kruskal-Wallis测试比较各组间SUVR的年化变化,并与认知评分(迷你精神状态检查、临床痴呆评定量表和阿尔茨海默病评估量表-认知亚量表)相关。使用Spearman ρ估计SUVR变化与认知结果之间的相关性。结果:基线18F-MK-6240 PET显示CU参与者的信号最小,MCI参与者的信号定位于内侧颞叶,AD参与者的信号跨越外侧颞叶并沿腹侧皮层向后延伸。纵向分析显示,CU、MCI和AD组MTC中tau沉积的年化百分比变化分别为0.17%±4.16、5.77%±2.97和4.31%±5.84 (P = 0.075)。CU、MCI和AD组tau沉积变化分别为0.00±0.05、0.10±0.07和0.12±0.16 (P = 0.039)。Tau积累与阿尔茨海默病评估量表-认知亚量表的下降相关(ρ = 0.43, P < 0.05)。结论:18F-MK-6240 PET追踪了tau蛋白随时间的积累,并提供了这些变化与认知能力下降相关的初步证据,支持其在纵向AD研究和试验设计中的应用,MTC有望成为临床试验的投资回报。
{"title":"Longitudinal Evaluation of 18F-MK-6240 Along the Alzheimer Disease Continuum.","authors":"Anna O Giarratana,Erin Jonaitis,Robert J Przybelski,Karly Cody,Tobey J Betthauser,Robert Cadman,Sara Frost Alberson,Bradley T Christian,Sterling C Johnson","doi":"10.2967/jnumed.125.271127","DOIUrl":"https://doi.org/10.2967/jnumed.125.271127","url":null,"abstract":"Understanding the rate of tau accumulation is critical for staging Alzheimer disease (AD), monitoring its progression, and informing clinical trial design. Although PET imaging with 18F-MK-6240, also known as florquinitau, can track tau pathology, longitudinal data remain limited. We evaluated longitudinal tau changes using 18F-MK-6240 PET across cognitive stages and analyzed regional rates of change with the goal of informing future clinical trial outcome measures. Methods: In this observational study, 27 participants with varying cognitive statuses (cognitively unimpaired [CU], mild cognitive impairment [MCI], and AD) underwent 18F-MK-6240 PET at baseline and at 6, 12, and 24 mo (or at 18 and 30 mo during the COVID-19 pandemic). Amyloid positivity at baseline was determined with 11C-labeled Pittsburgh compound B PET. Tau PET data were analyzed as SUV ratios (SUVRs) in regions of interest (ROIs) corresponding to Braak staging as well as the inferior temporal gyrus and 2 composite ROIs (metatemporal composite [MTC]) and an early tau composite. Annualized SUVR changes were compared across groups and correlated with cognitive scores (Mini-Mental State Examination, Clinical Dementia Rating Scale, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale) using the Kruskal-Wallis test. Correlations between the change in SUVR and cognitive outcomes were estimated using Spearman ρ. Results: Baseline 18F-MK-6240 PET showed a minimal signal in CU participants, localized signal to the medial temporal lobe in participants with MCI, and a signal spanning the inferolateral temporal lobe and extending posteriorly along the ventral cortex in participants with AD. Longitudinal analysis showed that the annualized percent change in tau deposition in the MTC was 0.17% ± 4.16, 5.77% ± 2.97, and 4.31% ± 5.84 in the CU, MCI, and AD groups, respectively (P = 0.075). The change in tau deposition was 0.00 ± 0.05, 0.10 ± 0.07, and 0.12 ± 0.16 in the CU, MCI, and AD groups, respectively (P = 0.039). Tau accumulation correlated with a decline on the Alzheimer Disease Assessment Scale-Cognitive Subscale (ρ = 0.43, P < 0.05). Conclusion: 18F-MK-6240 PET tracked tau accumulation over time and provided preliminary evidence that these changes correlate with cognitive decline, supporting its utility for longitudinal AD studies and trial design, with MTC emerging as a promising ROI for clinical trials.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detection of Focal Lesions in Epilepsy with [18F]UCB-H Synaptic Vesicle Protein 2A PET Imaging. [18F]UCB-H突触囊泡蛋白2A PET显像检测癫痫局灶性病变
Pub Date : 2026-04-02 DOI: 10.2967/jnumed.125.271505
Vanessa Pakula,Julia S Dorneich,Lukas Frontzkowski,Laura M Bartos,Nicholas Fearns,Sebastian N Roemer-Cassiano,Simon Lindner,Andreas Zwergal,Elisabeth Kaufmann,Günter Höglinger,Nicolai Franzmeier,Rudolf A Werner,Christian Vollmar,Jan Rémi,Matthias Brendel,Johannes Gnörich
Synaptic vesicle protein 2A (SV2A) is a universal marker of synaptic density. Recent advances in SV2A-targeted radiotracers have opened new windows into synaptic imaging. In focal epilepsy, synaptic dysfunction is a central pathologic feature. Unlike [18F]FDG PET, which reflects neuronal metabolism only indirectly, SV2A PET allows for direct quantification of synaptic density. We therefore evaluated [18F]UCB-H SV2A PET in comparison to [18F]FDG PET in patients with pharmacoresistant, unilateral focal epilepsy, aiming to assess its complementary value to established metabolic imaging. Methods: In total, 29 patients with unilateral focal epilepsy underwent both dynamic [18F]UCB-H PET (0-60 min) and static [18F]FDG PET (30-50 min) imaging. Eight patients were treated with the SV2A-binding medications levetiracetam or brivaracetam. [18F]UCB-H PET time-activity curves were extracted from 35 frames across cortical and subcortical regions, and Pearson correlation coefficients with [18F]FDG uptake were calculated for each frame to identify the most suitable imaging windows. Voxelwise percentage differences between epileptogenic and contralateral healthy hemispheres were computed to determine lesion severity and volume. Finally, we evaluated gaussian smoothing kernels for minimizing background noise while preserving contrast during lesion detection. Results: Treatment with SV2A-binding medications reduced late-phase [18F]UCB-H binding up to 75% compared with untreated individuals, demonstrating high target specificity. Framewise correlation analysis in unaffected contralateral hemispheres revealed significant associations between [18F]UCB-H and [18F]FDG uptake within the 0-10-min and 30-60-min postinjection intervals. These time windows were therefore selected for early- and late-phase analyses, respectively. Within epileptogenic foci, SV2A PET lesion severity correlated with [18F]FDG uptake for both early-phase (r = 0.61, P = 0.0042) and late-phase (r = 0.63, P = 0.0027) imaging. However, only early-phase SV2A PET lesion volume correlated with [18F]FDG lesion volume (r = 0.70, P = 0.0004), whereas late-phase SV2A PET volume did not. In line, [18F]FDG and early-phase [18F]UCB-H PET visually showed broad hypometabolic and hypoperfused areas around the epileptogenic zone, whereas late-phase [18F]UCB-H PET yielded sharper, high-contrast delineation of synaptic abnormalities. Conclusion: Dual-phase [18F]UCB-H PET provides complementary perfusion-like and synaptic information in focal epilepsy and shows spatial correspondence with [18F]FDG PET while offering more spatially confined synaptic signal changes.
突触囊泡蛋白2A (Synaptic vesicle protein 2A, SV2A)是突触密度的普遍标记物。靶向sv2a的放射性示踪剂的最新进展为突触成像打开了新的窗口。在局灶性癫痫中,突触功能障碍是一个主要的病理特征。与[18F]FDG PET仅间接反映神经元代谢不同,SV2A PET可以直接量化突触密度。因此,我们评估了[18F]UCB-H SV2A PET与[18F]FDG PET在耐药单侧局灶性癫痫患者中的对比,旨在评估其对既定代谢成像的补充价值。方法:29例单侧局灶性癫痫患者同时进行动态[18F]UCB-H PET (0-60 min)和静态[18F]FDG PET (30-50 min)成像。8例患者接受sv2a结合药物左乙拉西坦或布瓦西坦治疗。[18F]从35帧皮层和皮层下区域提取UCB-H PET时间活动曲线,并计算每帧与FDG摄取的Pearson相关系数[18F],以确定最合适的成像窗口。计算致痫性和对侧健康半球之间的体素百分比差异,以确定病变的严重程度和体积。最后,我们评估了高斯平滑核,以最小化背景噪声,同时在病变检测过程中保持对比度。结果:与未治疗个体相比,sv2a结合药物治疗可使晚期[18F]UCB-H结合减少75%,显示出高靶向特异性。对未受影响的对侧脑半球的框架相关分析显示,在注射后0-10分钟和30-60分钟的时间间隔内,[18F]UCB-H和[18F]FDG摄取之间存在显著关联。因此,这些时间窗口分别被选择用于早期和后期分析。在致痫灶内,SV2A PET病变严重程度与[18F]FDG早期(r = 0.61, P = 0.0042)和晚期(r = 0.63, P = 0.0027)成像相关。然而,只有早期SV2A PET病变体积与[18F]FDG病变体积相关(r = 0.70, P = 0.0004),而晚期SV2A PET体积不相关。与此一致的是,[18F]FDG和早期[18F]UCB-H PET在视觉上显示了癫痫区周围广泛的低代谢和低灌注区域,而晚期[18F]UCB-H PET显示了更清晰、高对比度的突触异常描绘。结论:双相[18F]UCB-H PET在局灶性癫痫中提供互补的灌注样和突触信息,与[18F]FDG PET在空间上呈现对应关系,同时提供更多空间受限的突触信号变化。
{"title":"Detection of Focal Lesions in Epilepsy with [18F]UCB-H Synaptic Vesicle Protein 2A PET Imaging.","authors":"Vanessa Pakula,Julia S Dorneich,Lukas Frontzkowski,Laura M Bartos,Nicholas Fearns,Sebastian N Roemer-Cassiano,Simon Lindner,Andreas Zwergal,Elisabeth Kaufmann,Günter Höglinger,Nicolai Franzmeier,Rudolf A Werner,Christian Vollmar,Jan Rémi,Matthias Brendel,Johannes Gnörich","doi":"10.2967/jnumed.125.271505","DOIUrl":"https://doi.org/10.2967/jnumed.125.271505","url":null,"abstract":"Synaptic vesicle protein 2A (SV2A) is a universal marker of synaptic density. Recent advances in SV2A-targeted radiotracers have opened new windows into synaptic imaging. In focal epilepsy, synaptic dysfunction is a central pathologic feature. Unlike [18F]FDG PET, which reflects neuronal metabolism only indirectly, SV2A PET allows for direct quantification of synaptic density. We therefore evaluated [18F]UCB-H SV2A PET in comparison to [18F]FDG PET in patients with pharmacoresistant, unilateral focal epilepsy, aiming to assess its complementary value to established metabolic imaging. Methods: In total, 29 patients with unilateral focal epilepsy underwent both dynamic [18F]UCB-H PET (0-60 min) and static [18F]FDG PET (30-50 min) imaging. Eight patients were treated with the SV2A-binding medications levetiracetam or brivaracetam. [18F]UCB-H PET time-activity curves were extracted from 35 frames across cortical and subcortical regions, and Pearson correlation coefficients with [18F]FDG uptake were calculated for each frame to identify the most suitable imaging windows. Voxelwise percentage differences between epileptogenic and contralateral healthy hemispheres were computed to determine lesion severity and volume. Finally, we evaluated gaussian smoothing kernels for minimizing background noise while preserving contrast during lesion detection. Results: Treatment with SV2A-binding medications reduced late-phase [18F]UCB-H binding up to 75% compared with untreated individuals, demonstrating high target specificity. Framewise correlation analysis in unaffected contralateral hemispheres revealed significant associations between [18F]UCB-H and [18F]FDG uptake within the 0-10-min and 30-60-min postinjection intervals. These time windows were therefore selected for early- and late-phase analyses, respectively. Within epileptogenic foci, SV2A PET lesion severity correlated with [18F]FDG uptake for both early-phase (r = 0.61, P = 0.0042) and late-phase (r = 0.63, P = 0.0027) imaging. However, only early-phase SV2A PET lesion volume correlated with [18F]FDG lesion volume (r = 0.70, P = 0.0004), whereas late-phase SV2A PET volume did not. In line, [18F]FDG and early-phase [18F]UCB-H PET visually showed broad hypometabolic and hypoperfused areas around the epileptogenic zone, whereas late-phase [18F]UCB-H PET yielded sharper, high-contrast delineation of synaptic abnormalities. Conclusion: Dual-phase [18F]UCB-H PET provides complementary perfusion-like and synaptic information in focal epilepsy and shows spatial correspondence with [18F]FDG PET while offering more spatially confined synaptic signal changes.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"120 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pulling Together: A 5-Year Plan to Improve Theranostic Outcomes by Improving the Accuracy of Dosimetry-An FNIH Joint Academic, Clinical, and Industrial Collaboration. 齐心协力:通过提高剂量测定的准确性来改善治疗结果的5年计划——FNIH联合学术、临床和工业合作。
Pub Date : 2026-04-02 DOI: 10.2967/jnumed.125.271665
Dale L Bailey,John C Dickson,Suzanne E Lapi,Carlos Uribe,Clarita Saldarriaga Vargas,Price Jackson,Caroline Stokke,Julia Brosch-Lenz,Althea Lang,Stephen A Graves,John J Sunderland
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引用次数: 0
Translation of Intraoperative Molecular Imaging for Clinical Use. 术中分子成像在临床应用中的翻译。
Pub Date : 2026-04-02 DOI: 10.2967/jnumed.124.268773
Lauren T Rosenblum,Arjun Pant,Catherine Yip,Gary Kohanbash,W Barry Edwards,Marcus M Malek
Intraoperative molecular imaging (IMI) is an evolving tool that enables targeted real-time visualization and delineation of tissue during surgery. IMI tracers can be fluorescent, radioactive, or dual-labeled. Their integration into the intraoperative setting is supported by several clinical trials, which led to Food and Drug Administration approval for a variety of these agents. Fluorescent tracers enable excellent spatial visualization, whereas radiotracers enable deep tissue detection, and dual-labeled tracers provide both. Novel activatable tracers that leverage properties of the tumor microenvironment are also being developed. Advances in imaging devices now permit IMI usage across diverse platforms, including minimally invasive surgery. Despite the limitations of autofluorescence, false-positive signals, and heterogeneity, the use of IMI continues to broaden in oncologic and nononcologic applications, driven by demonstrated improvements in surgical outcomes. In this review, we highlight the translation of IMI through clinical trials and future directions in IMI-guided surgery.
术中分子成像(IMI)是一种不断发展的工具,可以在手术过程中实现有针对性的实时可视化和组织描绘。IMI示踪剂可以是荧光的、放射性的或双重标记的。它们与术中环境的结合得到了几项临床试验的支持,这些试验导致食品和药物管理局批准了各种此类药物。荧光示踪剂可实现出色的空间可视化,而放射性示踪剂可实现深层组织检测,双标记示踪剂可同时提供这两种功能。利用肿瘤微环境特性的新型可激活示踪剂也正在开发中。成像设备的进步现在允许IMI在各种平台上使用,包括微创手术。尽管自身荧光、假阳性信号和异质性存在局限性,但由于手术结果的改善,IMI在肿瘤和非肿瘤领域的应用继续扩大。在这篇综述中,我们强调了IMI通过临床试验的转化和IMI引导手术的未来方向。
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引用次数: 0
Theranostics Explained: A Personalized Approach to Cancer Care. 治疗学解释:癌症治疗的个性化方法。
Pub Date : 2026-04-01 DOI: 10.2967/jnumed.125.271895
Alice F Viana,Elisa Cannarozzo
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引用次数: 0
Improving the Somatostatin Receptor Status Assessment for Personalized and Precise Management of Neuroendocrine Neoplasms with the Use of a 99mTc-Radiolabeled Somatostatin Receptor Antagonist: The Final Results of the ERA PerMed TECANT Clinical Trial. 使用99mtc放射标记的生长抑素受体拮抗剂改善生长抑素受体状态评估,以实现神经内分泌肿瘤的个性化和精确管理:ERA PerMed TECANT临床试验的最终结果
Pub Date : 2026-03-26 DOI: 10.2967/jnumed.125.270347
Alicja Hubalewska-Dydejczyk,Clemens Decristoforo,Renata Mikolajczak,Petra Kolenc,Marta Opalinska,Piotr Garnuszek,Konrad Skorkiewicz,Bogusław Glowa,Malgorzata Trofimiuk-Muldner,Andrej Studen,Urban Simoncic,Christine Rangger,Gianpaolo di Santo,Melpomeni Fani,Irene Virgolini,Luka Lezaic
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms in which an adequate expression of a somatostatin receptor (SSTR) serves as a target for imaging and therapy, typically using SSTR agonists. In the past decade, research in the field of NENs has focused on SSTR antagonists because of their higher and more sustained binding to a target, which may expand current diagnostic and therapeutic options, especially in patients with lower SSTR expression. The aim of this study was to perform a first-in-human injection of a novel 99mTc-labeled SSTR type 2 antagonist to establish safety, pharmacokinetics, and first assessment of SSTR status in patients with NENs through a qualitative and quantitative comparison with 68Ga-SSTR PET as a reference standard. Methods: Patients with metastatic grade 1 or 2 NENs and proven SSTR expression in primary and metastatic lesions on SSTR PET were imaged after a first-in-human injection of [99mTc]Tc-TECANT1. Assessment of safety, pharmacokinetics, and dosimetry was performed as a primary endpoint, with comparison of diagnostic performance and quantification of uptake to SSTR PET as a secondary endpoint. Results: Ten patients were enrolled. [99mTc]Tc-TECANT1 was found to be safe, with favorable pharmacokinetics and dosimetry (average total body effective dose of 3.3 ± 0.7 mSv). The diagnostic performance in comparison to that of SSTR PET was found to be superior, with a comparable or a higher number of detected lesions and superior target-to-background contrast (a factor of 2 and above for lesions with the highest uptake). Conclusion: [99mTc]Tc-TECANT1 appears to be a safe and widely utilizable radiopharmaceutical for the assessment of SSTR expression status in NENs. Validation of results in a larger cohort is warranted.
神经内分泌肿瘤(NENs)是一种异质性肿瘤,其中生长抑素受体(SSTR)的充分表达作为成像和治疗的靶点,通常使用SSTR激动剂。在过去的十年中,NENs领域的研究主要集中在SSTR拮抗剂上,因为它们与靶标的结合程度更高、更持久,这可能扩大目前的诊断和治疗选择,特别是在SSTR表达较低的患者中。本研究的目的是首次在人体内注射一种新型99mtc标记的2型SSTR拮抗剂,通过与68Ga-SSTR PET作为参考标准进行定性和定量比较,建立NENs患者的安全性、药代动力学,并首次评估SSTR状态。方法:首次在人体内注射[99mTc]Tc-TECANT1后,对转移性1级或2级NENs患者进行影像学检查,并在SSTR PET上证实原发和转移灶中有SSTR表达。安全性、药代动力学和剂量学评估作为主要终点,诊断性能的比较和对SSTR PET摄取的量化作为次要终点。结果:10例患者入组。[99mTc]Tc-TECANT1是安全的,具有良好的药代动力学和剂量学(平均全身有效剂量为3.3±0.7 mSv)。与SSTR PET相比,其诊断性能优越,检测到的病变数量相当或更高,目标与背景的对比也更好(对于摄取最高的病变,比为2及以上)。结论:[99mTc]Tc-TECANT1似乎是一种安全且广泛应用的放射性药物,可用于评估NENs中SSTR的表达状态。在更大的队列中验证结果是有必要的。
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引用次数: 0
Validation of Folate Receptor-α Selectivity of 6S-5-Methyltetrahydrofolate-Based Radioconjugates: A Prerequisite for Therapeutic Application? 基于6s -5-甲基四氢叶酸的放射缀合物叶酸受体-α选择性的验证:治疗应用的先决条件?
Pub Date : 2026-03-26 DOI: 10.2967/jnumed.125.271209
Ana Katrina Mapanao,Benjamin D Hunkeler,Giovanni Marzaro,Christian Vaccarin,Marco M Bühler,Roger Schibli,Niels J Rupp,Cristina Müller
The development of folic acid-based radioconjugates has been proposed for imaging and targeted radionuclide therapy of folate receptor-α (FRα)-positive cancer. Although folic acid binds both the tumor-associated FRα and the folate receptor-β (FRβ) expressed on certain blood cells, 6S-5-methyltetrahydrofolate (6S-5-MTHF) was reported to exhibit higher affinity for FRα. The aim of this study was, therefore, to investigate whether previously developed 6S-5-MTHF-based radioconjugates would preferentially bind to FRα. Methods: The 6R- and 6S-5-MTHF-based folate radioconjugates [177Lu]Lu-RedFol-1, [177Lu]Lu-RedFol-3, [177Lu]Lu-RedFol-24, and [177Lu]Lu-RedFol-25 were evaluated in vitro using transfected Chinese hamster ovary cells to assess their cell uptake and binding affinity to FRα expressed on RT16 cells and to FRβ expressed on D4 cells. Biodistribution and SPECT/CT imaging studies of the 5-MTHF-based radioconjugates were performed in a mouse model bearing both RT16 and D4 xenografts. Immunohistochemical staining was performed on selected patient-derived tissue sections of high-grade serous ovarian carcinoma, kidney, and bone marrow to provide a representative overview of FRα and FRβ expression. Results: The uptake and receptor binding affinity of 6R-5-MTHF-based radioconjugates were in the same range for RT16 and D4 cells, indicating comparable binding to the FRα and FRβ. The 6S-5-MTHF-based radioconjugates showed a 4-6-fold higher uptake in RT16 cells than in D4 cells, which can be ascribed to the 9-29-fold increased binding affinity to FRα than to FRβ. In vivo, the uptake of 6R-5-MTHF-based radioconjugates in RT16 and D4 xenografts reached 55%-73% IA/g and 25%-44% IA/g at 24 h after injection, respectively. The accumulation of 6S-5-MTHF-based radioconjugates in RT16 xenografts was 74%-100% IA/g, which was 9-21-fold higher than the 4%-10% IA/g uptake observed in D4 xenografts. Immunohistochemistry data confirmed high FRα expression in human ovarian cancer tissue sample and the presence of FRα in renal proximal tubules. In contrast, FRα was absent in human bone marrow, where FRβ was substantially expressed. Conclusion: This study confirmed that the use of 6S-5-MTHF-based radioconjugates can enable selective targeting of FRα. The high expression levels of FRα in ovarian cancer but absence in the bone marrow of human tissue samples infer therapeutic and safety benefits of using FRα-selective folate radioconjugates. Measures to reduce renal retention of 6S-5-MTHF radioconjugates may, however, still be necessary.
叶酸基放射缀合物已被提出用于叶酸受体-α (FRα)阳性癌症的成像和靶向放射性核素治疗。虽然叶酸结合肿瘤相关的FRα和叶酸受体β (FRβ)在某些血细胞上表达,但据报道,6s -5-甲基四氢叶酸(6S-5-MTHF)对FRα具有更高的亲和力。因此,本研究的目的是研究先前开发的基于6s -5- mthf的放射缀合物是否优先与FRα结合。方法:利用转染的中国仓鼠卵巢细胞,体外评价6R和6s -5- mthf为基础的叶酸放射偶联物[177Lu] lu - redfol1、[177Lu] lu - redfol3、[177Lu] lu - redfol24和[177Lu] lu - redfol25的细胞摄取和对RT16细胞上表达的FRα和D4细胞上表达的FRβ的结合亲和力。在携带RT16和D4异种移植物的小鼠模型中进行了基于5- mthf的放射缀合物的生物分布和SPECT/CT成像研究。免疫组织化学染色在患者来源的高级别浆液性卵巢癌、肾脏和骨髓组织切片上进行,以提供FRα和FRβ表达的代表性概述。结果:基于6r -5- mthf的放射性缀合物在RT16和D4细胞的摄取和受体结合亲和力在相同范围内,表明与FRα和FRβ的结合具有可比性。基于5s -5- mthf的放射缀合物在RT16细胞中的摄取比在D4细胞中高4-6倍,这可归因于与FRα的结合亲和力比与FRβ的结合亲和力高9-29倍。体内注射后24 h, RT16和D4异种移植物中基于6r -5- mthf的放射性缀合物的摄取分别达到55%-73% IA/g和25%-44% IA/g。RT16异种移植物中基于6s -5- mthf的放射性偶联物的积累量为74%-100% IA/g,比D4异种移植物中观察到的4%-10% IA/g高9-21倍。免疫组织化学数据证实,FRα在人卵巢癌组织样本中高表达,且FRα在肾近端小管中存在。相比之下,FRα在人骨髓中不存在,而FRβ在骨髓中大量表达。结论:本研究证实,使用基于6s -5- mthf的放射缀合物可以选择性靶向FRα。FRα在卵巢癌中高表达,但在人组织样本的骨髓中不存在,这表明使用FRα-选择性叶酸放射缀合物具有治疗和安全性方面的益处。然而,仍有必要采取措施减少6S-5-MTHF放射性缀合物的肾潴留。
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引用次数: 0
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The Journal of Nuclear Medicine
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