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Alpha Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors α肽受体核素治疗神经内分泌肿瘤
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.4274/nts.galenos.2023.0015
Gamze Beydağı, N. Alan Selçuk, L. Kabasakal
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引用次数: 0
Preclinical Evaluation of Novel PET Probes for Dementia 新型PET探针治疗痴呆症的临床前评价
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.03.004
Romy Cools MSc , Kobe Kerkhofs MSc , Renan C.F. Leitao PhD , Guy Bormans PhD

The development of novel PET imaging agents that selectively bind specific dementia-related targets can contribute significantly to accurate, differential and early diagnosis of dementia causing diseases and support the development of therapeutic agents. Consequently, in recent years there has been a growing body of literature describing the development and evaluation of potential new promising PET tracers for dementia. This review article provides a comprehensive overview of novel dementia PET probes under development, classified by their target, and pinpoints their preclinical evaluation pathway, typically involving in silico, in vitro and ex/in vivo evaluation. Specific target-associated challenges and pitfalls, requiring extensive and well-designed preclinical experimental evaluation assays to enable successful clinical translation and avoid shortcomings observed for previously developed ‘well-established’ dementia PET tracers are highlighted in this review.

选择性结合特定痴呆症相关靶点的新型PET显像剂的开发可以显著有助于痴呆症疾病的准确、鉴别和早期诊断,并支持治疗剂的开发。因此,近年来,越来越多的文献描述了潜在的新的有前景的痴呆症PET示踪剂的开发和评估。这篇综述文章全面概述了正在开发的新型痴呆PET探针,按其靶标进行分类,并确定了其临床前评估途径,通常涉及硅、体外和体外/体内评估。本综述强调了与特定靶点相关的挑战和陷阱,需要广泛且精心设计的临床前实验评估分析,以实现成功的临床转化,并避免先前开发的“成熟”痴呆PET示踪剂所观察到的缺陷。
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引用次数: 1
The Role of Alpha Therapy in Metastatic Castration Resistance Prostate Cancer α治疗在转移性去势抵抗性前列腺癌中的作用
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.4274/nts.galenos.2023.0014
N. Alan Selçuk, Kaan Akçay, L. Kabasakal
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引用次数: 0
Physical and Radiobiological Properties of Alpha Emitter Isotopes Used in Radionuclide Therapy 用于放射性核素治疗的α发射器同位素的物理和放射生物学特性
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.4274/nts.galenos.2023.0013
Türkay Toklu
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引用次数: 0
Academic integrity and artificial intelligence: is ChatGPT hype, hero or heresy? 学术诚信与人工智能:ChatGPT是炒作、英雄还是异端?
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.04.008
Geoffrey M. Currie PhD

Academic integrity in both higher education and scientific writing has been challenged by developments in artificial intelligence. The limitations associated with algorithms have been largely overcome by the recently released ChatGPT; a chatbot powered by GPT-3.5 capable of producing accurate and human-like responses to questions in real-time. Despite the potential benefits, ChatGPT confronts significant limitations to its usefulness in nuclear medicine and radiology. Most notably, ChatGPT is prone to errors and fabrication of information which poses a risk to professionalism, ethics and integrity. These limitations simultaneously undermine the value of ChatGPT to the user by not producing outcomes at the expected standard. Nonetheless, there are a number of exciting applications of ChatGPT in nuclear medicine across education, clinical and research sectors. Assimilation of ChatGPT into practice requires redefining of norms, and re-engineering of information expectations.

人工智能的发展对高等教育和科学写作的学术诚信提出了挑战。最近发布的ChatGPT在很大程度上克服了与算法相关的限制;一个由GPT-3.5提供支持的聊天机器人,能够实时对问题做出准确而人性化的回答。尽管有潜在的好处,但ChatGPT在核医学和放射学方面的实用性面临着巨大的局限。最值得注意的是,ChatGPT容易出现错误和信息捏造,这对专业精神、道德和诚信构成了风险。这些限制同时破坏了ChatGPT对用户的价值,因为它不能产生预期标准的结果。尽管如此,ChatGPT在教育、临床和研究部门的核医学中有许多令人兴奋的应用。将ChatGPT融入实践需要重新定义规范,并重新设计信息期望。
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引用次数: 23
Preclinical Imaging of Cardiovascular Disesase 心血管疾病的临床前影像学
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.04.004
Stephan G. Nekolla PhD , Christoph Rischpler MD , Takahiro Higuchi MD, PhD

Noninvasive imaging techniques, such as SPECT, PET, CT, echocardiography, or MRI, have become essential in cardiovascular research. They allow for the evaluation of biological processes in vivo without the need for invasive procedures. Nuclear imaging methods, such as SPECT and PET, offer numerous advantages, including high sensitivity, reliable quantification, and the potential for serial imaging. Modern SPECT and PET imaging systems, equipped with CT and MRI components in order to get access to morphological information with high spatial resolution, are capable of imaging a wide range of established and innovative agents in both preclinical and clinical settings. This review highlights the utility of SPECT and PET imaging as powerful tools for translational research in cardiology. By incorporating these techniques into a well-defined workflow- similar to those used in clinical imaging- the concept of “bench to bedside” can be effectively implemented.

非侵入性成像技术,如SPECT、PET、CT、超声心动图或MRI,已成为心血管研究中必不可少的技术。它们允许在体内评估生物过程,而不需要侵入性程序。核成像方法,如SPECT和PET,提供了许多优点,包括高灵敏度、可靠的定量和串行成像的潜力。现代SPECT和PET成像系统配备了CT和MRI组件,以获得具有高空间分辨率的形态信息,能够在临床前和临床环境中对广泛的已建立和创新药物进行成像。这篇综述强调了SPECT和PET成像作为心脏病学转化研究的强大工具的实用性。通过将这些技术结合到一个定义明确的工作流程中——类似于临床成像中使用的技术——可以有效地实现“从工作台到床边”的概念。
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引用次数: 1
FAPI-avid nonmalignant PET/CT findings: An expedited systematic review fapi非恶性PET/CT表现:快速系统回顾
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.02.001
Morten Bentestuen MD , Noor Al-Obaydi MD , Helle D. Zacho MD, PhD, DMSc

Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have demonstrated the superior sensitivity of FAPI PET/CT over fluorodeoxyglucose (FDG) PET/CT in several types of cancer. However, the cancer specificity of FAPI uptake remains understudied, and several cases of false-positive FAPI PET/CT findings have been reported.

A systematic search of PubMed, Embase, and Web of Science was conducted for studies published prior to April 2022 reporting nonmalignant FAPI PET/CT findings. We included original peer-reviewed articles of studies in humans using FAPI tracers radiolabeled with 68Ga or 18F that were published in English. Papers without original data and studies with insufficient information were excluded. Nonmalignant findings were presented on a per-lesion basis and grouped according to the type of organ or tissue involved. The search identified a total of 1.178 papers, of which 108 studies were eligible. Eighty studies were case reports (74%), and the remaining 28 were cohort studies (26%). A total of 2.372 FAPI-avid nonmalignant findings were reported, with the most frequent being uptake in the arteries, e.g., related to plaques (n = 1178, 49%). FAPI uptake was also frequently related to degenerative and traumatic bone and joint lesions (n = 147, 6%) or arthritis (n = 92, 4%). For organs, diffuse or focal uptake was often seen in cases of inflammation, infection, fibrosis, and IgG4-related disease (n = 157, 7%). FAPI-avid inflammatory/reactive lymph nodes (n = 121, 5%) and tuberculosis lesions (n = 51, 2%) have been reported and could prove to be potential pitfalls in cancer staging. Periodontitis (n = 76, 3%), hemorrhoids (n = 47, 2%), and scarring/wound healing (n = 35, 2%) also presented as focal uptake on FAPI PET/CT. The present review provides an overview of the reported FAPI-avid nonmalignant PET/CT findings to date. A large number of benign clinical entities may show FAPI uptake and should be kept in mind when interpreting FAPI PET/CT findings in patients with cancer.

成纤维细胞活化蛋白抑制剂(FAPI)在肿瘤学正电子发射断层扫描/计算机断层扫描(PET/CT)中是一种很有前途的示踪剂。大量研究表明,在几种类型的癌症中,FAPI PET/CT优于氟脱氧葡萄糖(FDG)PET/CT。然而,FAPI摄取的癌症特异性仍然研究不足,并且已经报道了几个假阳性FAPIPET/CT结果的病例。对PubMed、Embase和Web of Science进行了系统搜索,以查找2022年4月之前发表的报告非恶性FAPI PET/CT发现的研究。我们纳入了以英文发表的使用68Ga或18F放射性标记的FAPI示踪剂进行人体研究的原始同行评审文章。没有原始数据的论文和信息不足的研究被排除在外。未对准的发现以每个病变为基础,并根据所涉及的器官或组织类型进行分组。检索共发现1.178篇论文,其中108项研究符合条件。80项研究为病例报告(74%),其余28项为队列研究(26%)。共报告了2.372例FAPI狂热的非恶性发现,其中最常见的是动脉摄取,例如与斑块有关(n = 1178、49%)。FAPI摄取也经常与退行性和创伤性骨和关节病变有关(n = 147、6%)或关节炎(n = 92.4%)。对于器官,在炎症、感染、纤维化和IgG4相关疾病(n = 157、7%)。FAPI狂热的炎症/反应性淋巴结(n = 121,5%)和肺结核病变(n = 51,2%)已经被报道并且可能被证明是癌症分期的潜在陷阱。牙周炎(n = 76.3%)、痔疮(n = 47.2%)和瘢痕形成/伤口愈合(n = 35.2%)也表现为FAPI PET/CT上的局灶摄取。本综述概述了迄今为止报道的FAPI狂热的非恶性PET/CT发现。大量良性临床实体可能显示FAPI摄取,在解释癌症患者的FAPI PET/CT结果时应牢记这一点。
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引用次数: 11
Preclinical Development in Radiopharmaceutical Therapy for Prostate Cancer 前列腺癌放射药物治疗的临床前研究进展
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.06.007
Suresh Alati PhD , Rajan Singh PhD , Martin G. Pomper MD, PhD , Steven P. Rowe MD, PhD , Sangeeta Ray Banerjee PhD

Prostate cancer is a leading cause of cancer death in men worldwide. Among the various treatment options, radiopharmaceutical therapy has shown notable success in metastatic, castration-resistant disease. Radiopharmaceutical therapy is a systemic approach that delivers cytotoxic radiation doses precisely to the malignant tumors and/or tumor microenvironment. Therapeutic radiopharmaceuticals are composed of a therapeutic radionuclide and a high-affinity, tumor-targeting carrier molecule. Therapeutic radionuclides used in preclinical prostate cancer studies are primarily α-, β-, or Auger-electron-emitting radiometals or radiohalogens. Monoclonal antibodies, antibody-derived fragments, peptides, and small molecules are frequently used as tumor-targeting molecules. Over the years, several important membrane-associated proteases and receptors have been identified, validated, and subsequently used for preclinical radiotherapeutic development for prostate cancer. Prostate-specific membrane antigen (PSMA) is the most well-studied prostate cancer-associated protease in preclinical literature. PSMA-targeting radiotherapeutic agents are being investigated using high-affinity antibody- and small-molecule-based agents for safety and efficacy. Early generations of such agents were developed simply by replacing radionuclides of the imaging agents with therapeutic ones. Later, extensive structure-activity relationship studies were conducted to address the safety and efficacy issues obtained from initial patient data. Recent regulatory approval of the 177Lu-labeled low-molecular-weight agent, 177Lu-PSMA-617, is a significant accomplishment. Current preclinical experiments are focused on the structural modification of 177Lu-PSMA-617 and relevant investigational agents to increase tumor targeting and reduce off-target binding and toxicity in healthy organs. While lutetium-177 (177Lu) remains the most widely used radionuclide, radiolabeled analogs with iodine-131 (128I), yttrium-90 (89Y), copper-67 (67Cu), and terbium-161 (161Tb) have been evaluated as potential alternatives in recent years. In addition, agents carrying the α-particle-emitting radiohalogen, astatine-211 (211At), or radiometals, actinium-225 (225Ac), lead-212 (212Pb), radium-223 (223Ra), and thorium-227 (227Th), have been increasingly investigated in preclinical research. Besides PSMA-based radiotherapeutics, other prominent prostate cancer-related proteases, for example, human kallikrein peptidases (HK2 and HK3), have been explored using monoclonal-antibody-(mAb)-based targeting platforms. Several promising mAbs targeting receptors overexpressed on the different stages of prostate cancer have a

前列腺癌症是全球男性癌症死亡的主要原因。在各种治疗方案中,放射药物治疗在转移性、去势抵抗性疾病中取得了显著成功。放射药物治疗是一种系统性方法,可以精确地向恶性肿瘤和/或肿瘤微环境提供细胞毒性辐射剂量。治疗性放射性药物由治疗性放射性核素和高亲和力肿瘤靶向载体分子组成。临床前前列腺癌症研究中使用的治疗性放射性核素主要是α-、β−-或俄歇电子发射的放射性金属或放射性卤素。单克隆抗体、抗体衍生片段、肽和小分子经常用作肿瘤靶向分子。多年来,几种重要的膜相关蛋白酶和受体已被鉴定、验证,并随后用于癌症的临床前放射治疗开发。前列腺特异性膜抗原(PSMA)是临床前文献中研究最全面的前列腺癌相关蛋白酶。PSMA靶向放射治疗药物正在使用基于高亲和力抗体和小分子的药物进行安全性和有效性研究。早期的这类试剂只是通过用治疗试剂代替成像试剂中的放射性核素而开发出来的。后来,进行了广泛的结构-活性关系研究,以解决从初始患者数据中获得的安全性和有效性问题。最近177Lu标记的低分子量试剂177Lu-PSMA-617的监管批准是一项重大成就。目前的临床前实验集中在177Lu-PSMA-617和相关研究药物的结构修饰上,以增加肿瘤靶向性,减少健康器官中的脱靶结合和毒性。虽然镥-177(177Lu)仍然是使用最广泛的放射性核素,但近年来,碘-131(128I)、钇-90(89Y)、铜-67(67Cu)和铽-161(161Tb)的放射性标记类似物已被评估为潜在的替代品。此外,在临床前研究中,越来越多地研究了携带发射放射性卤素的α-粒子的试剂,即astatine-211(211At)或放射性金属,锕-225(225Ac)、铅212(212Pb)、镭-223(223Ra)和钍-227(227Th)。除了基于PSMA的放射治疗外,还使用基于单克隆抗体(mAb)的靶向平台探索了其他突出的前列腺癌相关蛋白酶,例如人激肽释放酶肽酶(HK2和HK3)。靶向在癌症不同阶段过表达的受体的几种有前景的mAb也已被开发用于放射性药物治疗,例如Delta-like配体3(DLL-3)、CD46和含CUB结构域的蛋白1(CDCP1)。胃泌素释放肽受体(GRPR)是一种在局限性和转移性前列腺癌中表达的成熟的膜相关受体,使用基于肽的靶向平台也取得了进展。此外,机制驱动的联合治疗似乎是临床前前列腺癌症放射治疗的一个新兴领域。在此,我们回顾了与前列腺癌症临床前放射药物治疗相关的最新进展。这些内容概括为两个主要主题:(1)治疗性放射性核素和(2)使用单克隆抗体、小分子和肽的肿瘤靶向方法。
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引用次数: 2
Preclinical Imaging Studies: Protocols, Preparation, Anesthesia, and Animal Care 临床前影像学研究:方案、准备、麻醉和动物护理
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.02.003
Aage K.O. Alstrup DVM, PhD , Mie R. Dollerup , Mette I.T. Simonsen , Mikkel H. Vendelbo MD, PhD

Today preclinical PET imaging connects laboratory research with clinical applications. Here PET clearly bridges the gap, as nearly identical imaging protocols can be applied to both animal and humans. However, some hurdles exist and researchers must be careful, partly because the animals are usually anesthetized during the scans, while human volunteers are awake. This review is based on our own experiences of some of the most important pitfalls and how to overcome them. This includes how studies should be designed, how to select the right anesthesia and monitoring. The choice of anesthesia is quite crucial, as it may have a greater influence on the results than the effect of the tested procedures. Monitoring is necessary, as the animals cannot fully maintain homeostasis during anesthesia, and reliable results are dependent on a stable physiology. Additionally, it is important to note that rodents, in particular, are prone to rapidly becoming hypothermic. Thus, the selection of an appropriate anesthetic and monitoring protocol is crucial for both obtaining accurate results and ensuring animal welfare. Prior to imaging, catheters for tracer administration and, if necessary, blood sampling should be implanted. The administration of tracers should be done in a manner that minimizes interference with the scans, and the same applies to any serial blood sampling. The limited blood volume and organ size of rodents should also be taken into consideration when planning experiments. Finally, if the animal needs to be awakened after the scan, proper care must be taken to ensure their welfare.

如今,临床前PET成像将实验室研究与临床应用联系起来。在这里,PET清楚地弥合了这一差距,因为几乎相同的成像协议可以应用于动物和人类。然而,存在一些障碍,研究人员必须小心,部分原因是动物在扫描过程中通常被麻醉,而人类志愿者是清醒的。这篇综述是基于我们自己对一些最重要的陷阱以及如何克服它们的经验。这包括如何设计研究,如何选择正确的麻醉和监测。麻醉的选择非常关键,因为它对结果的影响可能比测试程序的效果更大。监测是必要的,因为动物在麻醉期间不能完全保持体内平衡,可靠的结果取决于稳定的生理学。此外,值得注意的是,啮齿类动物尤其容易迅速体温过低。因此,选择合适的麻醉剂和监测方案对于获得准确的结果和确保动物福利至关重要。成像前,应植入示踪剂给药导管,如有必要,还应植入血液取样导管。示踪剂的使用应尽量减少对扫描的干扰,这同样适用于任何系列血液采样。在计划实验时,还应考虑啮齿动物有限的血容量和器官大小。最后,如果扫描后需要唤醒动物,必须采取适当的护理措施,以确保它们的福利。
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引用次数: 2
Preclinical Research Highlighting Contemporary Targeting Mechanisms of Radiolabelled Compounds for PET Based Infection Imaging 临床前研究强调了基于PET的感染成像放射标记化合物的当代靶向机制
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1053/j.semnuclmed.2023.03.001
Janke Kleynhans PhD , Mike Machaba Sathekge MD, PhD , Thomas Ebenhan PhD

It is important to constantly monitor developments in the preclinical imaging arena of infection. Firstly, novel radiopharmaceuticals with the correct characteristics must be identified to funnel into the clinic. Secondly, it must be evaluated if enough innovative research is being done and adequate resources are geared towards the development of radiopharmaceuticals that could feed into the Nuclear Medicine Clinic in the near future. It is proposed that the ideal infection imaging agent will involve PET combined with CT but more ideally MRI. The radiopharmaceuticals currently presented in preclinical literature have a wide selection of vectors and targets. Ionic formulations of PET-radionuclides such 64CuCl2 and 68GaCl2 are evaluated for bacterial infection imaging. Many small molecule based radiopharmaceuticals are being investigated with the most prominent targets being cell wall synthesis, maltodextrin transport (such as [18F]F-maltotriose), siderophores (bacterial and fungal infections), the folate synthesis pathway (such as [18F]F-PABA) and protein synthesis (radiolabelled puromycin). Mycobacterial specific antibiotics, antifungals and antiviral agents are also under investigation as infection imaging agents. Peptide based radiopharmaceuticals are developed for bacterial, fungal and viral infections. The radiopharmaceutical development could even react quickly enough on a pandemic to develop a SARS-CoV-2 imaging agent in a timely fashion ([64Cu]Cu-NOTA-EK1). New immuno-PET agents for the imaging of viruses have recently been published, specifically for HIV persistence but also for SARS-CoV2. A very promising antifungal immuno-PET agent (hJ5F) is also considered. Future technologies could include the application of aptamers and bacteriophages and even going as far as the design of theranostic infection. Another possibility would be the application of nanobodies for immuno-PET applications. Standardization and optimization of the preclinical evaluation of radiopharmaceuticals could enhance clinical translation and reduce time spent in pursuing less than optimal candidates.

不断监测感染的临床前成像领域的发展是很重要的。首先,必须识别出具有正确特征的新型放射性药物才能进入临床。其次,必须评估是否正在进行足够的创新研究,是否有足够的资源用于开发放射性药物,这些药物可能在不久的将来进入核医学诊所。有人提出,理想的感染成像剂将包括PET和CT,但更理想的是MRI。目前在临床前文献中介绍的放射性药物具有广泛的载体和靶标选择。评估PET放射性核素的离子制剂,例如64CuCl2和68GaCl2,用于细菌感染成像。许多基于小分子的放射性药物正在研究中,最突出的靶点是细胞壁合成、麦芽糊精转运(如[18F]F-麦芽三糖)、铁载体(细菌和真菌感染)、叶酸合成途径(如[14F]F-PABA)和蛋白质合成(放射性标记的嘌呤霉素)。分枝杆菌特异性抗生素、抗真菌药物和抗病毒药物作为感染显像剂也在研究中。基于肽的放射性药物被开发用于细菌、真菌和病毒感染。放射性药物的开发甚至可以对大流行做出足够快的反应,及时开发出严重急性呼吸系统综合征冠状病毒2型显像剂([64Cu]Cu-NOTA-EK1)。最近发表了用于病毒成像的新的免疫PET试剂,特别是用于HIV持续性,也用于严重急性呼吸系统综合征冠状病毒2型。还考虑了一种非常有前景的抗真菌免疫PET剂(hJ5F)。未来的技术可能包括适体和噬菌体的应用,甚至包括治疗感染的设计。另一种可能性是纳米体在免疫PET应用中的应用。放射性药物临床前评估的标准化和优化可以增强临床转化,减少寻找不太理想候选药物的时间。
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引用次数: 2
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Seminars in nuclear medicine
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