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Ongoing Clinical Phase Studies of Targeted Alpha Therapies 靶向α治疗正在进行的临床阶段研究
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.4274/nts.galenos.2023.0018
Onur Erdem Şahin
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引用次数: 0
Special Challenges in PET Imaging of Ectothermic Vertebrates 异温脊椎动物PET成像的特殊挑战
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.06.006
Aage Kristian Olsen Alstrup DVM, PhD , Morten Busk PhD , Anita Dittrich MS , Kasper Hansen PhD , Tobias Wang PhD , Mads Damkjær PhD , Johnnie Bremholm Andersen PhD , Henrik Lauridsen PhD

The bulk of biomedical positron emission tomography (PET)-scanning experiments are performed on mammals (ie, rodents, pigs, and dogs), and the technique is only infrequently applied to answer research questions in ectothermic vertebrates such as fish, amphibians, and reptiles. Nevertheless, many unique and interesting physiological characteristics in these ectothermic vertebrates could be addressed in detail through PET. The low metabolic rate of ectothermic animals, however, may compromise the validity of physiological and biochemical parameters derived from the images created by PET and other scanning modalities. Here, we review some of the considerations that should be taken into account when PET scanning fish, amphibians, and reptiles. We present specific results from our own experiments, many of which remain previously unpublished, and we draw on examples from the literature. We conclude that knowledge on the natural history and physiology of the species studied and an understanding of the limitations of the PET scanning techniques are necessary to avoid the design of faulty experiments and erroneous conclusions.

大部分生物医学正电子发射断层扫描(PET)扫描实验都是在哺乳动物(如啮齿动物、猪和狗)身上进行的,该技术很少用于回答鱼类、两栖动物和爬行动物等体外脊椎动物的研究问题。然而,这些体外热脊椎动物的许多独特而有趣的生理特征可以通过PET详细解决。然而,体外热动物的低代谢率可能会损害从PET和其他扫描模式创建的图像中得出的生理和生化参数的有效性。在这里,我们回顾了PET扫描鱼类、两栖动物和爬行动物时应考虑的一些因素。我们展示了我们自己的实验的具体结果,其中许多实验之前尚未发表,我们还引用了文献中的例子。我们得出的结论是,有必要了解所研究物种的自然历史和生理学,并了解PET扫描技术的局限性,以避免设计错误的实验和错误的结论。
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引用次数: 1
Nuclear Medicine Preclinical Research: The Role of Cell Cultures 核医学临床前研究:细胞培养的作用
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.04.007
Morten Busk PhD , Steffen Sinning PhD , Aage K.O. Alstrup DVM, PhD, Dr.Vet.Sci , Ole L. Munk PhD , Mikkel H. Vendelbo MD, PhD

Cell lines are essential in biomedical research due to their adaptability and precise simulation of physiological and pathophysiological conditions. Cell culture techniques have greatly advanced our understanding of biology in various fields and are widely regarded as a reliable and durable tool. Their diverse applications make them indispensable in scientific research. Radiation-emitting compounds are commonly used in cell culture research to investigate biological processes. Radiolabeled compounds are utilized to study cell function, metabolism, molecular markers, receptor density, drug binding and kinetics, as well as to analyze the direct interaction of radiotracers with target organ cells. This allows for the examination of normal physiology and disease states. The In Vitro system simplifies the study and filters out nonspecific signals from the In Vivo environment, leading to more specific results. Moreover, cell cultures offer ethical advantages when evaluating new tracers and drugs in preclinical studies. While cell experiments cannot entirely replace animal experiments, they reduce the need for live animals in experimentation.

细胞系由于其适应性和对生理和病理生理条件的精确模拟而在生物医学研究中至关重要。细胞培养技术极大地促进了我们在各个领域对生物学的理解,并被广泛认为是一种可靠和耐用的工具。它们的多样应用使它们在科学研究中不可或缺。发射辐射的化合物通常用于细胞培养研究,以研究生物过程。放射性标记的化合物用于研究细胞功能、代谢、分子标记物、受体密度、药物结合和动力学,以及分析放射性示踪剂与靶器官细胞的直接相互作用。这允许检查正常的生理和疾病状态。体外系统简化了研究,并从体内环境中过滤出非特异性信号,从而产生更具体的结果。此外,在临床前研究中评估新的示踪剂和药物时,细胞培养提供了伦理优势。虽然细胞实验不能完全取代动物实验,但它们减少了实验中对活体动物的需求。
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引用次数: 1
Preclinical Imaging of Prostate Cancer 前列腺癌的临床前影像学
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.02.002
Colleen Olkowski BS , Bruna Fernandes PhD , Gary L. Griffiths PhD , Frank Lin MD , Peter L. Choyke MD

Prostate cancer remains a major cause of mortality and morbidity, affecting millions of men, with a large percentage expected to develop the disease as they reach advanced ages. Treatment and management advances have been dramatic over the past 50 years or so, and one aspect of these improvements is reflected in the multiple advances in diagnostic imaging techniques. Much attention has been focused on molecular imaging techniques that offer high sensitivity and specificity and can now more accurately assess disease status and detect recurrence earlier. During development of molecular imaging probes, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) must be evaluated in preclinical models of the disease. If such agents are to be translated to the clinic, where patients undergoing these imaging modalities are injected with a molecular imaging probe, these agents must first be approved by the FDA and other regulatory agencies prior to their adoption in clinical practice. Scientists have worked assiduously to develop preclinical models of prostate cancer that are relevant to the human disease to enable testing of these probes and related targeted drugs. Challenges in developing reproducible and robust models of human disease in animals are beset with practical issues such as the lack of natural occurrence of prostate cancer in mature male animals, the difficulty of initiating disease in immune-competent animals and the sheer size differences between humans and conveniently smaller animals such as rodents. Thus, compromises in what is ideal and what can be achieved have had to be made. The workhorse of preclinical animal models has been, and remains, the investigation of human xenograft tumor models in athymic immunocompromised mice. Later models have used other immunocompromised models as they have been found and developed, including the use of directly derived patient tumor tissues, completely immunocompromised mice, orthotopic methods for inducing prostate cancer within the mouse prostate itself and metastatic models of advanced disease. These models have been developed in close parallel with advances in imaging agent chemistries, radionuclide developments, computer electronics advances, radiometric dosimetry, biotechnologies, organoid technologies, advances in in vitro diagnostics, and overall deeper understandings of disease initiation, development, immunology, and genetics. The combination of molecular models of prostatic disease with radiometric-based studies in small animals will always remain spatially limited due to the inherent resolution sensitivity limits of PET and SPECT decay processes, fundamentally set at around a 0.5 cm resolution limit. Nevertheless, it is central to researcher's efforts and to successful clinical translation that the best animal models are adopted, accepted, and scientifically verified as part of this truly interdisciplinary approach to addressing this important disea

前列腺癌症仍然是导致死亡和发病的主要原因,影响着数百万男性,其中很大一部分人预计会在年老时患上这种疾病。在过去50年左右的时间里,治疗和管理取得了巨大的进步,这些进步的一个方面反映在诊断成像技术的多项进步中。分子成像技术提供了高灵敏度和特异性,现在可以更准确地评估疾病状态并更早地发现复发。在分子成像探针的开发过程中,必须在疾病的临床前模型中评估单光子发射计算机断层扫描(SPECT)和正电子发射断层扫描(PET)。如果要将这些药物转化为临床,在临床上给接受这些成像模式的患者注射分子成像探针,这些药物在临床应用之前必须首先获得美国食品药品监督管理局和其他监管机构的批准。科学家们一直在努力开发与人类疾病相关的前列腺癌症临床前模型,以便能够测试这些探针和相关靶向药物。在动物中开发可复制和稳健的人类疾病模型面临的挑战受到了实际问题的困扰,如成年雄性动物缺乏前列腺癌症的自然发生,免疫能力强的动物难以引发疾病,以及人类与啮齿动物等方便的较小动物之间的巨大体型差异。因此,必须在理想和可以实现的目标上做出妥协。临床前动物模型的主力军一直是,现在仍然是,在无胸腺免疫受损小鼠中研究人类异种移植物肿瘤模型。后来的模型使用了已经发现和开发的其他免疫功能低下的模型,包括使用直接来源的患者肿瘤组织、完全免疫功能低下小鼠、在小鼠前列腺内诱导前列腺癌症的原位方法以及晚期疾病的转移模型。这些模型的开发与显像剂化学、放射性核素发展、计算机电子学发展、辐射剂量测定、生物技术、类器官技术、体外诊断的进步以及对疾病发生、发展、免疫学和遗传学的全面深入理解密切相关。由于PET和SPECT衰变过程固有的分辨率灵敏度限制,前列腺疾病的分子模型与基于放射性的小动物研究的结合将始终保持空间限制,基本上设置在0.5厘米左右的分辨率限制。然而,作为解决这一重要疾病的真正跨学科方法的一部分,采用、接受和科学验证最佳动物模型是研究人员努力和成功临床翻译的核心。
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引用次数: 3
Targeted Alpha Therapy - Promising Radionuclides Beyond Ac-225 靶向α治疗-有前途的放射性核素超越Ac-225
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.4274/nts.galenos.2023.0017
M. Ocak, L. Kabasakal
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引用次数: 0
Radium-223 for the Treatment of Painful Bone Metastates in Castration-resistant Prostate Cancer 镭-223治疗去势抵抗性前列腺癌疼痛性骨转移
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.4274/nts.galenos.2023.0016
Elif Özdemir
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引用次数: 0
A Clinical Role of PET-MRI in Prostate Cancer? PET-MRI在前列腺癌中的临床作用?
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-08-29 DOI: 10.1053/j.semnuclmed.2023.08.001
Michael C.M. Gammel MD, Esteban L. Solari PhD, Matthias Eiber MD, Isabel Rauscher MD, Stephan G. Nekolla PhD

PET/MRI is a relevant application field for prostate cancer management, offering advantages in early diagnosis, staging, and therapy planning. Despite drawbacks such as higher costs, longer acquisition time, and the need for skilled personnel, the technical integration of PET and MRI provides valuable information for detecting primary tumors, identifying metastases, and characterizing the disease, leading to more accurate staging and personalized treatment strategies. However, PET/MRI adoption has been slow, but ongoing technological advancements and AI integration might overcome challenges and improve clinical utility. As precision medicine gains importance in oncology, PET/MRI's multiparametric data can tailor treatment plans to individual patients, providing a comprehensive assessment of tumor biology and aggressiveness for more effective therapeutic strategies.

PET/MRI是前列腺癌治疗的相关应用领域,在早期诊断、分期和治疗计划方面具有优势。尽管存在成本较高、获取时间较长以及需要熟练人员等缺点,PET和MRI的技术整合为检测原发肿瘤、识别转移和表征疾病提供了有价值的信息,从而导致更准确的分期和个性化治疗策略。然而,PET/MRI的采用一直缓慢,但持续的技术进步和人工智能集成可能会克服挑战并提高临床应用。随着精准医学在肿瘤学中的重要性日益增加,PET/MRI的多参数数据可以为个体患者量身定制治疗计划,为更有效的治疗策略提供肿瘤生物学和侵袭性的全面评估。
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引用次数: 0
[15O]H2O PET: Potential or Essential for Molecular Imaging? [15O]H2O PET:分子成像的潜力还是必要条件?
IF 4.6 2区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Pub Date : 2023-08-26 DOI: 10.1053/j.semnuclmed.2023.08.002

Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome.

人体水路成像是精确测量流向不同器官的血流量的绝佳方法。这使其成为一种强大的诊断工具,可用于治疗与血流灌注和氧合有关的多种疾病。虽然水 PET 的历史悠久,但其真正的潜力尚未进入常规临床实践。这篇文章强调了水 PET 在分子成像方面的潜力,并指出它有望成为 21 世纪精准医学从临床前研究到临床研究和实践等不同领域的重要工具。最近在高灵敏度 PET 成像方面取得的技术进步可以为这项技术的发展起到关键的加速作用,尽管仍有一些挑战需要克服。
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引用次数: 0
Is There a Role of Interim PSMA PET in Chemotherapy of Prostate Cancer? PSMA PET在前列腺癌化疗中是否有作用?
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-08-18 DOI: 10.1053/j.semnuclmed.2023.07.006
Riccardo Laudicella PhD , Matteo Bauckneht PhD , Irene A. Burger

While RECIST 1.1 is well established in radiological response assessment, it is of limited use in prostate cancer (PCa) considering that the disease is often seen only as sclerotic bone changes on conventional imaging. Therefore, a molecular imaging-based response assessment including bone scans has been proposed and used in clinical trials, however, due to the flare phenomenon on bone scans this assessment leads to substantial delays in the detection of progression. Indeed, a robust and reliable imaging tool to assess response to chemotherapy in PCa is still warranted. Whether Positron Emission Tomography (PET) targeting the Prostate-Specific Membrane Antigen (PSMA) could achieve this, is still controversial. In this review, we summarized the available data on cytotoxic agents and their impact on PSMA expression, as well as the available data on PSMA PET imaging for response assessment.

虽然RECIST 1.1在放射反应评估中已经建立,但在前列腺癌(PCa)中的应用有限,因为该疾病在常规影像学上通常仅被视为硬化性骨改变。因此,包括骨扫描在内的基于分子成像的反应评估已被提出并用于临床试验,然而,由于骨扫描的耀斑现象,这种评估导致了进展检测的严重延迟。的确,一种稳健可靠的成像工具来评估前列腺癌患者对化疗的反应仍然是必要的。针对前列腺特异性膜抗原(PSMA)的正电子发射断层扫描(PET)能否实现这一目标仍存在争议。在这篇综述中,我们总结了细胞毒性药物及其对PSMA表达影响的现有数据,以及用于评估PSMA反应的PET成像数据。
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引用次数: 0
Bone Metastasis in Prostate Cancer: Bone Scan Versus PET Imaging 前列腺癌骨转移:骨扫描与PET成像
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-08-17 DOI: 10.1053/j.semnuclmed.2023.07.004
Nasibeh Mohseninia MD , Nazanin Zamani-Siahkali MD , Sara Harsini MD, PHD , Ghasemali Divband MD , Christian Pirich MD, PHD , Mohsen Beheshti MD

Prostate cancer is the second most common cause of malignancy among men, with bone metastasis being a significant source of morbidity and mortality in advanced cases. Detecting and treating bone metastasis at an early stage is crucial to improve the quality of life and survival of prostate cancer patients. This objective strongly relies on imaging studies. While CT and MRI have their specific utilities, they also possess certain drawbacks. Bone scintigraphy, although cost-effective and widely available, presents high false-positive rates. The emergence of PET/CT and PET/MRI, with their ability to overcome the limitations of standard imaging methods, offers promising alternatives for the detection of bone metastasis. Various radiotracers targeting cell division activity or cancer-specific membrane proteins, as well as bone seeking agents, have been developed and tested. The use of positron-emitting isotopes such as fluorine-18 and gallium-68 for labeling allows for a reduced radiation dose and unaffected biological properties. Furthermore, the integration of artificial intelligence (AI) and radiomics techniques in medical imaging has shown significant advancements in reducing interobserver variability, improving accuracy, and saving time. This article provides an overview of the advantages and limitations of bone scan using SPECT and SPECT/CT and PET imaging methods with different radiopharmaceuticals and highlights recent developments in hybrid scanners, AI, and radiomics for the identification of prostate cancer bone metastasis using molecular imaging.

前列腺癌是男性恶性肿瘤的第二大常见原因,在晚期病例中,骨转移是发病率和死亡率的重要来源。早期发现和治疗骨转移对提高前列腺癌患者的生活质量和生存率至关重要。这一目标强烈依赖于影像学研究。虽然CT和MRI有其特定的用途,但它们也有一定的缺点。骨显像虽然具有成本效益且广泛可用,但存在较高的假阳性率。PET/CT和PET/MRI的出现,克服了标准成像方法的局限性,为骨转移的检测提供了有希望的替代方法。各种针对细胞分裂活性或癌症特异性膜蛋白的放射性示踪剂以及寻骨剂已经开发和测试。使用诸如氟-18和镓-68等正电子发射同位素进行标记,可以减少辐射剂量并不影响生物特性。此外,医学成像中人工智能(AI)和放射组学技术的整合在减少观察者之间的差异、提高准确性和节省时间方面取得了重大进展。本文概述了利用SPECT、SPECT/CT和PET成像方法与不同放射性药物进行骨扫描的优点和局限性,并重点介绍了混合扫描仪、人工智能和放射组学在利用分子成像识别前列腺癌骨转移方面的最新进展。
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Seminars in nuclear medicine
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