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Active monitoring improves radiopharmaceutical administration quality. 主动监测提高了放射性药物给药质量
Pub Date : 2023-03-07 eCollection Date: 2023-01-01 DOI: 10.3389/fnume.2023.1126029
James R Crowley, Iryna Barvi, Jackson W Kiser

Introduction: In 2016, our center adopted technology to routinely monitor 18F-FDG radiopharmaceutical administrations. Within six months of following basic quality improvement methodology, our technologists reduced extravasation rates from 13.3% to 2.9% (p < 0.0001). These same technologists administer other radiopharmaceuticals (without monitoring technology) for general nuclear medicine procedures in a separate facility at the clinic. Our hypothesis was that they would apply 18F-FDG lessons-learned to 99mTc-MDP administrations and that 99mTc-MDP manual injection extravasation rate would be consistent with the ongoing 18F-FDG manual injection extravasation rate (3.4%). We tested our hypothesis by following the same quality improvement methodology and added monitoring equipment to measure extravasation rates for 99mTc-MDP administrations.

Results: 816 99mTc-MDP administrations were monitored during 16-month period (four 4-month periods: A, B, C, D). Period A (first four months of active monitoring) extravasation rate was not statistically different from the Measure Phase extravasation rate of the previously completed PET/CT QI Project: 12.75% compared to 13.3% (p-0.7925). Period A extravasation rate was statistically different from Period C (months 9-12) extravasation rate and Period D (months 13-16) extravasation rate: 12.75% compared to 2.94% and to 3.43% (p < 0.0001). During Period C and D technologists achieved extravasation rates comparable to the longstanding manual 18F-FDG injection extravasation rate (3.4%).

Conclusion: Our initial hypothesis, that awareness of a problem and the steps need to correct it would result in process improvement, was not accurate. While those factors are important, they are not sufficient. Our findings suggest that active monitoring and the associated display of results are critical to quality improvement efforts to reduce and sustain radiopharmaceutical extravasation rates.

2016年,我中心采用技术对18F-FDG放射性药物管理进行常规监测。在遵循基本质量改进方法的六个月内,我们的技术人员将外渗率从13.3%降低到2.9% (p < 0.0001)。这些技术人员在诊所的单独设施中为一般核医学程序管理其他放射性药物(没有监测技术)。我们的假设是,他们将18F-FDG的经验教训应用于99mTc-MDP给药,99mTc-MDP手动注射外渗率将与正在进行的18F-FDG手动注射外渗率(3.4%)一致。我们通过遵循相同的质量改进方法和增加监测设备来测量99mTc-MDP药物的外渗率来检验我们的假设。结果共监测816例99mTc-MDP用药16个月(4个月:A、B、C、D)。A期(主动监测的前四个月)外渗率与之前完成PET/CT QI项目的Measure期外渗率无统计学差异:12.75%比13.3% (p = 0.7925)。A期外渗率与C期(9 ~ 12个月)外渗率、D期(13 ~ 16个月)外渗率分别为12.75%、2.94%和3.43%,差异有统计学意义(p < 0.0001)。在C和D期间,技术人员实现了与长期手工18F-FDG注射外渗率相当的外渗率(3.4%)。我们最初的假设是,意识到问题和纠正问题的步骤将导致过程改进,这是不准确的。虽然这些因素很重要,但它们是不够的。我们的研究结果表明,积极监测和相关结果的显示对于降低和维持放射性药物外渗率的质量改进工作至关重要。
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引用次数: 0
Extravasation of radiopharmaceuticals: Why report? 放射性药物外渗:为什么要报道?
Pub Date : 2023-03-06 eCollection Date: 2023-01-01 DOI: 10.3389/fnume.2023.1148177
Thomas L Morgan

In this essay, I wish to discuss extravasation in the context of medical imaging and therapy with radiopharmaceuticals. Central to this discussion are two facts. First, they are easily identified, but the frequency of significant extravasations is unclear because there is no generally accepted definition of such an event. And second, there appears to be few reports of injuries from these events. The central thesis of this essay is that these events should be reported and followed so that agreement can be reached on the definition of a "significant" event which should be classified as a medical event in accordance with US Nuclear Regulatory Commission (NRC) regulations. I will also outline steps that can be taken to reduce the risk of extravasations.

在这篇文章中,我希望在医学成像和放射性药物治疗的背景下讨论外渗。这场讨论的核心是两个事实。首先,它们很容易识别,但严重外渗的频率尚不清楚,因为对此类事件没有公认的定义。其次,似乎很少有关于这些事件造成人员受伤的报道。本文的中心论点是,应该报告和遵循这些事件,以便就“重大”事件的定义达成一致,根据美国核管理委员会(NRC)的规定,该事件应被归类为医疗事件。我还将概述可以采取的措施,以减少超支的风险。
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引用次数: 0
Radiomics insight into the neurodegenerative "hot" brain: A narrative review from the nuclear medicine perspective. 放射组学对神经退行性“热”大脑的洞察:从核医学角度的叙述性综述
Pub Date : 2023-02-27 eCollection Date: 2023-01-01 DOI: 10.3389/fnume.2023.1143256
Gayane Aghakhanyan, Gianfranco Di Salle, Salvatore Claudio Fanni, Roberto Francischello, Dania Cioni, Mirco Cosottini, Duccio Volterrani, Emanuele Neri

The application of radiomics for non-oncologic diseases is currently emerging. Despite its relative infancy state, the evidence highlights the potential of radiomics approaches to serve as neuroimaging biomarkers in the field of the neurodegenerative brain. This systematic review presents the last progress and potential application of radiomics in the field of neurodegenerative nuclear imaging applied to positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) by focusing mainly on the two most common neurodegenerative disorders, Alzheimer's (AD) and Parkinson's disease (PD). A comprehensive review of the current literature was performed using the PubMed and Web of Science databases up to November 2022. The final collection of eighteen relevant publications was grouped as AD-related and PD-related. The main efforts in the field of AD dealt with radiomics-based early diagnosis of preclinical AD and the prediction of MCI to AD conversion, meanwhile, in the setting of PD, the radiomics techniques have been used in the attempt to improve the assessment of PD diagnosis, the differential diagnosis between PD and other parkinsonism, severity assessment, and outcome prediction. Although limited evidence with relatively small cohort studies, it seems that radiomics-based analysis using nuclear medicine tools, mainly [18F]Fluorodeoxyglucose (FDG) and β-amyloid (Aβ) PET, and dopamine transporter (DAT) SPECT, can be used for computer-aided diagnoses in AD-continuum and parkinsonian disorders. Combining nuclear radiomics analysis with clinical factors and introducing a multimodality approach can significantly improve classification and prediction efficiency in neurodegenerative disorders.

放射组学在非肿瘤疾病中的应用目前正在兴起。尽管其处于相对婴儿期,但证据突出了放射组学方法在神经退行性脑领域作为神经成像生物标志物的潜力。本系统综述了放射组学在神经退行性核成像领域的最新进展和潜在应用,主要集中在阿尔茨海默病(AD)和帕金森病(PD)这两种最常见的神经退行性疾病上,应用于正电子发射断层扫描(PET)和单光子发射计算机断层扫描(SPECT)。截至2022年11月,使用PubMed和Web of Science数据库对当前文献进行了全面综述。最终收集的18种相关出版物分为AD相关出版物和PD相关出版物。AD领域的主要工作涉及基于放射组学的临床前AD早期诊断和MCI向AD转化的预测,同时,在PD的背景下,放射组学技术已被用于改善PD诊断的评估、PD与其他帕金森病的鉴别诊断、严重程度评估和结果预测。尽管相对较小的队列研究证据有限,但使用核医学工具(主要是[18F]氟脱氧葡萄糖(FDG)和β-淀粉样蛋白(Aβ)PET以及多巴胺转运蛋白(DAT)SPECT)进行的基于放射组学的分析似乎可用于AD连续体和帕金森病的计算机辅助诊断。将核放射组学分析与临床因素相结合,并引入多模态方法,可以显著提高神经退行性疾病的分类和预测效率。
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引用次数: 0
PET tracers in glioblastoma: Toward neurotheranostics as an individualized medicine approach. 胶质母细胞瘤的PET示踪剂:作为一种个体化医学方法的神经修复术
Pub Date : 2023-02-27 eCollection Date: 2023-01-01 DOI: 10.3389/fnume.2023.1103262
Habibullah Dadgar, Narges Jokar, Reza Nemati, Mykol Larvie, Majid Assadi

Over the past decade, theragnostic radiopharmaceuticals have been used in nuclear medicine for both diagnosis and treatment of various tumors. In this review, we carried out a literature search to investigate and explain the role of radiotracers in the theragnostic approach to glioblastoma multiform (GBM). We primarily focused on basic and rather common positron emotion tomography (PET) radiotracers in these tumors. Subsequently, we introduced and evaluated the preclinical and clinical results of theranostic-based biomarkers including integrin receptor family, prostate-specific membrane antigen (PSMA), fibroblast activated protein (FAP), somatostatin receptors (SRS), and chemokine receptor-4 (CXCR4) for patients with GBM to confer the benefit of personalized therapy. Moreover, promising research opportunities that could have a profound impact on the treatment of GBM over the next decade are also highlighted. Preliminary results showed the potential feasibility of the theragnostic approach using theses biomarkers in GBM patients.

在过去的十年中,放射性治疗药物已被用于核医学中各种肿瘤的诊断和治疗。在这篇综述中,我们进行了文献检索,以调查和解释放射性示踪剂在多形性胶质母细胞瘤(GBM)的诊断方法中的作用。我们主要关注这些肿瘤的基本和相当常见的正电子情感断层扫描(PET)放射性示踪剂。随后,我们介绍并评估了基于治疗学的生物标志物的临床前和临床结果,包括整合素受体家族、前列腺特异性膜抗原(PSMA)、成纤维细胞活化蛋白(FAP)、生长抑素受体(SRS)和趋化因子受体-4 (CXCR4),以确定个性化治疗的益处。此外,还强调了未来十年可能对GBM治疗产生深远影响的有希望的研究机会。初步结果表明,在GBM患者中使用这些生物标志物进行治疗的方法具有潜在的可行性。
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引用次数: 0
Transparency - a patient-centric view on radiopharmaceutical extravasations. 透明度——以患者为中心的放射性药物外渗观点
Pub Date : 2023-02-27 eCollection Date: 2023-01-01 DOI: 10.3389/fnume.2023.1127692
Pam Kohl

Most radiopharmaceuticals are intravenously administered during nuclear medicine imaging or therapy procedures. When a nuclear medicine clinician delivers some or all of a radioactive drug into a patient's healthy tissue rather than the vein as intended, a patient experiences an extravasation. Radiopharmaceutical extravasations provide zero patient benefit and considerable potential downsides, depending on the severity of the extravasations. What nuclear medicine patients want and need regarding the administration of radiopharmaceuticals is transparency. And yet in the year 2023, little transparency exists regarding these extravasations. From the patient perspective, transparency regarding extravasations is essential to improving care, ensuring radiation protection, reducing health inequities, and untangling the deeply disturbing and irregular relationship between the nuclear medicine community and their regulating body, The U.S. Nuclear Regulatory Commission. Transparency is also critical to help address many other questions regarding radiopharmaceutical extravasations.

大多数放射性药物是在核医学成像或治疗过程中静脉注射的。当核医学临床医生将部分或全部放射性药物输送到患者的健康组织中,而不是按预期输送到静脉中时,患者会出现外渗。根据外渗的严重程度,放射性药物外渗对患者没有任何益处,也有相当大的潜在负面影响。核医学患者在放射性药物管理方面想要和需要的是透明度。然而,在2023年,这些挥霍几乎没有透明度。从患者的角度来看,外渗的透明度对于改善护理、确保辐射防护、减少健康不平等以及解决核医学界与其监管机构美国核监管委员会之间令人深感不安和不规则的关系至关重要。透明度对于帮助解决有关放射性药物外渗的许多其他问题也至关重要。
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引用次数: 0
Case report: Efficacy of lutetium-177 oxodotreotide for neuroendocrine tumor with central nervous system metastases. 病例报告:黄体177氧曲肽治疗中枢神经系统转移的神经内分泌肿瘤疗效
Pub Date : 2023-02-23 eCollection Date: 2023-01-01 DOI: 10.3389/fnume.2023.1074948
Nwanneka Okwundu, Christopher R Weil, Heloisa P Soares, Gabriel C Fine, Donald M Cannon

Neuroendocrine tumors (NETs) rarely metastasize to the brain. However, when they occur, NET brain metastases are associated with a poor prognosis. Due to their low incidence, NET brain metastases are poorly studied, with few data to guide a consensus for management. Prior reports have documented treatment with chemotherapy, resection, whole brain radiation therapy, and stereotactic radiosurgery, all with low rates of survival. We present a case of a patient with type 3 well-differentiated gastric NET with widespread metastatic disease, including central nervous system lesions in the pineal gland and left cerebellopontine angle (CPA), which were avid on 68Ga-dotatate positron emission tomography. The patient received four doses of 200 mCi (7.4 GBq) lutetium-177 oxodotreotide (177Lu-dotatate) administered every 8 weeks over the course of 6 months. The treatments provided local control of the pineal and CPA lesions for 23 months until the development of diffuse leptomeningeal progression that necessitated further therapies. 177Lu-dotatate may be a viable treatment for local control of NET brain metastases. More studies are needed to validate its efficacy in this clinical scenario.

神经内分泌肿瘤很少转移到大脑。然而,当它们发生时,NET脑转移与预后不良有关。由于NET脑转移的发生率较低,因此对其研究很少,很少有数据可以指导一致的治疗。先前的报告记录了化疗、切除、全脑放射治疗和立体定向放射外科的治疗,所有这些都具有低生存率。我们报告了一例3型高分化胃NET患者,该患者患有广泛的转移性疾病,包括松果体和左桥小脑角的中枢神经系统病变,他们热衷于68Ga dotatate正电子发射断层扫描。病人接受了四剂200 mCi(7.4 GBq)在6个月的过程中每8周给药一次的镥-177氧代多曲肽(177Lu dotatate)。治疗对松果体和CPA病变进行了23个月的局部控制,直到出现弥漫性软脑膜进展,需要进一步治疗。177Lu dotatate可能是一种可行的局部控制NET脑转移的治疗方法。需要更多的研究来验证其在这种临床情况下的疗效。
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引用次数: 0
A heterogeneous phantom study for investigating the stability of PET images radiomic features with varying reconstruction settings. 一项研究不同重建设置下PET图像放射学特征稳定性的异质幻像研究
Pub Date : 2023-02-14 eCollection Date: 2023-01-01 DOI: 10.3389/fnume.2023.1078536
Emad Alsyed, Rhodri Smith, Lee Bartley, Christopher Marshall, Emiliano Spezi

The purpose of this work was to assess the capability of radiomic features in distinguishing PET image regions with different uptake patterns. Furthermore, we assessed the stability of PET radiomic features with varying image reconstruction settings. An in-house phantom was designed and constructed, consisting of homogenous and heterogenous artificial phantom inserts. Four artificially constructed inserts were placed into a water filled phantom and filled with varying levels of radioactivity to simulate homogeneous and heterogeneous uptake patterns. The phantom was imaged for 80 min. PET images were reconstructed whilst varying reconstruction parameters. The parameters adjusted included, number of ordered subsets, number of iterations, use of time-of-flight and filter cut off. Regions of interest (ROI) were established by segmentation of the phantom inserts from the reconstructed images. In total seventy eight 3D radiomic features for each ROI with unique reconstructed parameters were extracted. The Friedman test was used to determine the statistical power of each radiomic feature in differentiating phantom inserts with different hetero/homogeneous configurations. The Coefficient of Variation (COV) of each feature, with respect to the reconstruction setting was used to determine feature stability. Forty three out of seventy eight radiomic features were found to be stable (COV 5%) against all reconstruction settings. To provide any utility, stable features are required to differentiate between regions with different hetro/homogeneity. Of the forty three stable features, fifteen (35%) features showed a statistically significant difference between the artificially constructed inserts. Such features included GLCM (Difference average, Difference entropy, Dissimilarity and Inverse difference), GLRL (Long run emphasis, Grey level non uniformity and Run percentage) and NGTDM (Complexity and Strength). The finding of this work suggests that radiomic features are capable of distinguishing between radioactive distribution patterns that demonstrate different levels of heterogeneity. Therefore, radiomic features could serve as an adjuvant diagnostic tool along with traditional imaging. However, the choice of the radiomic features needs to account for variability introduced when different reconstruction settings are used. Standardization of PET image reconstruction settings across sites performing radiomic analysis in multi-centre trials should be considered.

这项工作的目的是评估放射学特征在区分具有不同摄取模式的PET图像区域方面的能力。此外,我们评估了不同图像重建设置下PET放射学特征的稳定性。设计并构建了一个内部体模,由同质和异质的人造体模插入物组成。将四个人工构建的插入物放入一个充满水的模型中,并填充不同水平的放射性,以模拟均匀和不均匀的摄取模式。体模成像80 在改变重建参数的同时重建PET图像。调整的参数包括有序子集的数量、迭代次数、飞行时间的使用和滤波器截止。通过从重建图像中分割体模插入物来建立感兴趣区域(ROI)。总共提取了具有唯一重建参数的每个ROI的78个3D放射学特征。Friedman检验用于确定每个放射学特征在区分具有不同异质/同质配置的体模插入物方面的统计功效。每个特征相对于重建设置的变异系数(COV)用于确定特征稳定性。在所有重建设置中,78个放射学特征中有43个是稳定的(COV≤5%)。为了提供任何效用,需要稳定的特征来区分具有不同hetro/同质性的区域。在43个稳定特征中,15个(35%)特征在人工构建的插入物之间显示出统计学上的显著差异。这些特征包括GLCM(差异平均值、差异熵、差异性和反向差异)、GLRL(长期强调、灰度不均匀性和运行百分比)和NGTDM(复杂性和强度)。这项工作的发现表明,放射学特征能够区分不同程度异质性的放射性分布模式。因此,放射组学特征可以作为传统成像的辅助诊断工具。然而,放射组学特征的选择需要考虑到当使用不同的重建设置时引入的可变性。应考虑在多中心试验中进行放射组学分析的各个部位的PET图像重建设置的标准化。
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引用次数: 0
Pulmonary artery stenosis in Takayasu disease mimicking pulmonary embolism on perfusion lung scan: A case report. 肺灌注扫描模拟肺栓塞的高松病肺动脉狭窄1例
Pub Date : 2023-02-10 eCollection Date: 2023-01-01 DOI: 10.3389/fnume.2023.1122046
Chaimae Sebbar, Soufiane Hiroual, Nathalie Kouassi, Mohamed Aziz Bsiss, Aboubaker Matrane

Lung scan is an accurate and noninvasive tool for evaluating the distribution of lung perfusion. We present a rare case of total absence of perfusion on lung scan to the right lung with two contralateral defects due to severe occlusion of the right pulmonary artery, as well as segmental arteries in the left lung in a young female woman diagnosed with Takayasu Arteritis. We highlight the similarities of the findings between pulmonary arteritis in Takayasu disease and thromboembolic disease and the importance of careful interpretation of perfusion lung scan in order to avoid misdiagnosis that could endanger the patient's life.

肺部扫描是一种准确、无创的评估肺部灌注分布的工具。我们报告了一例罕见的右肺肺部扫描完全没有灌注的病例,该病例中一名年轻女性被诊断为大动脉炎,由于右肺动脉和左肺节段动脉严重闭塞,导致对侧两处缺损。我们强调了大动脉炎与血栓栓塞性疾病的相似性,以及仔细解释灌注肺扫描的重要性,以避免可能危及患者生命的误诊。
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引用次数: 0
A multi-object deep neural network architecture to detect prostate anatomy in T2-weighted MRI: Performance evaluation. 在T2加权MRI中检测前列腺解剖结构的多对象深度神经网络结构:性能评估
Pub Date : 2023-02-06 eCollection Date: 2022-01-01 DOI: 10.3389/fnume.2022.1083245
Maria Baldeon-Calisto, Zhouping Wei, Shatha Abudalou, Yasin Yilmaz, Kenneth Gage, Julio Pow-Sang, Yoganand Balagurunathan

Prostate gland segmentation is the primary step to estimate gland volume, which aids in the prostate disease management. In this study, we present a 2D-3D convolutional neural network (CNN) ensemble that automatically segments the whole prostate gland along with the peripheral zone (PZ) (PPZ-SegNet) using a T2-weighted sequence (T2W) of Magnetic Resonance Imaging (MRI). The study used 4 different public data sets organized as Train #1 and Test #1 (independently derived from the same cohort), Test #2, Test #3 and Test #4. The prostate gland and the peripheral zone (PZ) anatomy were manually delineated with consensus read by a radiologist, except for Test #4 cohorts that had pre-marked glandular anatomy. A Bayesian hyperparameter optimization method was applied to construct the network model (PPZ-SegNet) with a training cohort (Train #1, n = 150) using a five-fold cross validation. The model evaluation was performed on an independent cohort of 283 T2W MRI prostate cases (Test #1 to #4) without any additional tuning. The data cohorts were derived from The Cancer Imaging Archives (TCIA): PROSTATEx Challenge, Prostatectomy, Repeatability studies and PROMISE12-Challenge. The segmentation performance was evaluated by computing the Dice similarity coefficient and Hausdorff distance between the estimated-deep-network identified regions and the radiologist-drawn annotations. The deep network architecture was able to segment the prostate gland anatomy with an average Dice score of 0.86 in Test #1 (n = 192), 0.79 in Test #2 (n = 26), 0.81 in Test #3 (n = 15), and 0.62 in Test #4 (n = 50). We also found the Dice coefficient improved with larger prostate volumes in 3 of the 4 test cohorts. The variation of the Dice scores from different cohorts of test images suggests the necessity of more diverse models that are inclusive of dependencies such as the gland sizes and others, which will enable us to develop a universal network for prostate and PZ segmentation. Our training and evaluation code can be accessed through the link: https://github.com/mariabaldeon/PPZ-SegNet.git.

前列腺分割是估计前列腺体积的主要步骤,有助于前列腺疾病的管理。在这项研究中,我们提出了一种2D-3D卷积神经网络(CNN)集合,该集合使用磁共振成像(MRI)的T2加权序列(T2W)自动分割整个前列腺和外周区(PZ)(PPZ-SegNet)。该研究使用了4个不同的公共数据集,分别组织为第1列和第1列测试(独立于同一队列)、第2列测试、第3列测试和第4列测试。前列腺和外周区(PZ)解剖结构由放射科医生通过一致阅读手动描绘,具有预先标记的腺体解剖结构的测试#4队列除外。应用贝叶斯超参数优化方法构建具有训练队列(Train#1,n = 150)使用五倍交叉验证。在没有任何额外调整的情况下,对283例T2W MRI前列腺病例的独立队列进行模型评估(测试#1至#4)。数据队列来源于癌症成像档案(TCIA):PROSTATEx挑战、前列腺切除术、重复性研究和PROMISE12挑战。通过计算Dice相似系数和估计的深度网络识别区域与放射科医生绘制的注释之间的Hausdorff距离来评估分割性能。深度网络结构能够分割前列腺解剖结构,在测试#1(n = 192),测试#2中的0.79(n = 26),试验#3中的0.81(n = 15) ,和测试#4中的0.62(n = 50)。我们还发现,在4个测试队列中的3个队列中,随着前列腺体积的增大,Dice系数有所改善。不同测试图像组的Dice评分的变化表明,有必要建立更多样的模型,包括腺体大小等依赖性,这将使我们能够开发一个用于前列腺和PZ分割的通用网络。我们的培训和评估代码可以通过以下链接访问:https://github.com/mariabaldeon/PPZ-SegNet.git.
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引用次数: 0
Proof of lung muscarinic receptor occupancy by tiotropium: Translational Positron Emission Tomography studies in non-human primates and humans. 噻托溴铵占用肺毒蕈碱受体的证据:非人类灵长类动物和人类的转化正电子发射断层扫描研究
Pub Date : 2023-01-18 eCollection Date: 2022-01-01 DOI: 10.3389/fnume.2022.1080005
Zsolt Cselényi, Aurelija Jucaite, Pär Ewing, Per Stenkrona, Cecilia Kristensson, Peter Johnström, Magnus Schou, Martin Bolin, Christer Halldin, Bengt Larsson, Ken Grime, Ulf G Eriksson, Lars Farde

Introduction: Molecular imaging has not been used to support the development of drugs for the treatment of pulmonary disorders. The aim of the present translational study was to advance quantitative pulmonary PET imaging by demonstrating occupancy of the reference asthma drug tiotropium at muscarinic acetylcholine receptors (mAChR).

Methods: PET imaging was performed using the muscarinic radioligand [11C]VC-002. The key methodological step involved estimating muscarinic receptor binding while disentangling it from the background of non-specific binding. The relationship between tiotropium exposure and receptor occupancy (RO) was assessed in non-human primates (NHPs) after intravenous injection of tiotropium doses at a broad dose interval (0.03-1 µg/kg). The feasibility of measuring RO in the human lung was then confirmed in seven healthy human subjects after inhalation of a single therapeutic dose of tiotropium (18 µg).

Results: There was an evident effect of tiotropium on [11C]VC-002 binding to mAChRs in lungs in both NHPs and humans. In NHPs, RO was 11 to 78% and increased in a dose dependent manner. Non-displaceable binding in NHPs was about 10% of total binding. In humans, RO was 6%-65%, and non-displaceable binding was about 20% of total binding at baseline.

Discussion: The results demonstrate that [11C]VC-002 binds specifically to mAChRs in the lungs enabling the assessment of RO following administration of muscarinic antagonist drugs. Furthermore, the methodology has potential not only for dose finding and comparison of drug formulations in future applied studies, but also for evaluating changes in lung receptor distribution during disease or in response to therapy.

Clinical trial registration: ClinicalTrials.gov, identifier: NCT03097380.

引言分子成像尚未用于支持治疗肺部疾病的药物的开发。本转化研究的目的是通过证明参考哮喘药物噻托溴铵在毒蕈碱乙酰胆碱受体(mAChR)上的占有率来推进定量肺PET成像。方法使用毒蕈碱放射性配体[11C]VC-002进行PET成像。关键的方法学步骤涉及估计毒蕈碱受体的结合,同时将其从非特异性结合的背景中解开。在非人类灵长类动物(NHP)中,以宽剂量间隔(0.03-1 µg/kg)。7名健康受试者在吸入单一治疗剂量的噻托溴铵(18 µg)。结果噻托溴铵对[11C]VC-002在NHP和人肺中与mAChRs结合有明显影响。在NHP中,RO为11%至78%,并以剂量依赖的方式增加。NHP中的不可置换结合约占总结合的10%。在人类中,RO为6%-65%,不可置换结合约为基线时总结合的20%。讨论结果表明[11C]VC-002与肺中的mAChRs特异性结合,从而能够在给予毒蕈碱拮抗剂药物后评估RO。此外,该方法不仅有可能在未来的应用研究中发现剂量和比较药物配方,而且有可能评估疾病期间或治疗后肺部受体分布的变化。临床试验注册ClinicalTrials.gov,标识符:NCT03097380。
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Frontiers in nuclear medicine (Lausanne, Switzerland)
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