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与某些肿瘤学和非肿瘤学应用相关的转化(放射性)药物研究综述。

An overview of translational (radio)pharmaceutical research related to certain oncological and non-oncological applications.

作者信息

Cona Marlein Miranda, de Witte Peter, Verbruggen Alfons, Ni Yicheng

机构信息

Marlein Miranda Cona, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, B-3000 Leuven, Belgium.

出版信息

World J Methodol. 2013 Dec 26;3(4):45-64. doi: 10.5662/wjm.v3.i4.45.

Abstract

Translational medicine pursues the conversion of scientific discovery into human health improvement. It aims to establish strategies for diagnosis and treatment of diseases. Cancer treatment is difficult. Radio-pharmaceutical research has played an important role in multiple disciplines, particularly in translational oncology. Based on the natural phenomenon of necrosis avidity, OncoCiDia has emerged as a novel generic approach for treating solid malignancies. Under this systemic dual targeting strategy, a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin ((123)I-Hyp), a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation. In this review, by emphasizing the potential clinical applicability of OncoCiDia, we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution, dosimetry, pharmacokinetic and, chemical and radiochemical toxicities of the preparations. Myocardial infarction is a global health problem. Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability, searching for diagnostic imaging agents with authentic necrosis avidity is pursued. Therefore, a comparative study on the biological profiles of the necrosis avid (123)I-Hyp and the commercially available (99m)Tc-Sestamibi was conducted and the results are demonstrated. Cholelithiasis or gallstone disease may cause gallbladder inflammation, infection and other severe complications. While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives, their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones. The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented. Multiple uses of automatic contrast injectors may reduce costs and save resources. However, cross-contaminations with blood-borne pathogens of infectious diseases may occur. We developed a radioactive method for safety evaluation of a new replaceable patient-delivery system. By mimicking pathogens with a radiotracer, we assessed the feasibility of using the system repeatedly without septic risks. This overview is deemed to be interesting to those involved in the related fields for translational research.

摘要

转化医学致力于将科学发现转化为人类健康的改善。其旨在建立疾病的诊断和治疗策略。癌症治疗颇具难度。放射性药物研究在多个学科中发挥了重要作用,尤其是在转化肿瘤学领域。基于坏死亲和力这一自然现象,OncoCiDia已成为一种治疗实体恶性肿瘤的新型通用方法。在这种系统性双靶点策略下,一种血管破坏剂首先选择性地引发大量肿瘤坏死,随后是碘 - 131标记的金丝桃素((123)I - Hyp),一种坏死亲和性化合物,它通过β辐射的交叉火力效应杀死残留的癌细胞。在本综述中,通过强调OncoCiDia潜在的临床适用性,我们总结了我们的研究活动,包括放射性碘化金丝桃素Hyp制剂的优化以及该制剂的生物分布、剂量学、药代动力学以及化学和放射化学毒性的近期研究。心肌梗死是一个全球性的健康问题。尽管使用放射性灌注示踪剂的心脏闪烁扫描用于评估心肌活力,但人们仍在寻找具有真正坏死亲和力的诊断成像剂。因此,我们对坏死亲和性(123)I - Hyp和市售(99m)Tc - sestamibi的生物学特性进行了比较研究,并展示了结果。胆石症或胆结石疾病可能会引发胆囊炎、感染及其他严重并发症。在研究Hyp及其衍生物坏死亲和力的潜在机制时,利用了它们天然存在的荧光团特性来靶向作为胆结石主要成分的胆固醇。研究了Hyp作为胆石症光学成像剂的效用并展示了结果。自动造影剂注射器的多次使用可能会降低成本并节省资源。然而,可能会发生与传染病血源性病原体的交叉污染。我们开发了一种用于新型可替换患者给药系统安全性评估的放射性方法。通过用放射性示踪剂模拟病原体,我们评估了重复使用该系统而无感染风险的可行性。本综述被认为对参与相关转化研究领域的人员具有吸引力。

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