Gutfilen Bianca, Souza Sergio Al, Valentini Gianluca
Department of Radiology, School of Medicine, Laboratório de Marcação de Células e Moléculas (LMCM), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil,
Advanced Center Oncology Macerata (ACOM), Montecosaro, Italy.
Drug Des Devel Ther. 2018 Oct 2;12:3235-3245. doi: 10.2147/DDDT.S170879. eCollection 2018.
Ongoing studies of physiological and pathological processes have led to a corresponding need for new radiopharmaceuticals, especially when studies are limited by the absence of a particular radiolabeled target. Thus, the development of new radioactive tracers is highly relevant and can represent a significant contribution to efforts to elucidate important phenomena in biology. Currently, theranostics represents a new frontier in the fields of medicine and nuclear medicine, with the same compound being used for both diagnosis and treatment. In the human body, copper (Cu) is the third most abundant metal and it plays a crucial role in many biological functions. Correspondingly, in various acquired and inherited pathological conditions, such as cancer and Alzheimer's disease, alterations in Cu levels have been found. Moreover, a wide spectrum of neurodegenerative disorders are associated with higher or lower levels of Cu, as well as inappropriately bound or distributed levels of Cu in the brain. In human cells, the membrane protein, hCtr1, binds Cu in its Cu(I) oxidation state in an energy-dependent manner. Copper-64 (Cu) is a cyclotron-produced radionuclide that has exhibited physical properties that are complementary for diagnosis and/or therapeutic purposes. To date, very few reports have described the clinical development of Cu as a radiotracer for cancer imaging. In this review, we highlight recent insights in our understanding and use of CuCl as a theranostic agent for various types of tumors. To the best of our knowledge, no adverse effects or clinically observable pharmacological effects have been described for CuCl in the literature. Thus, Cu represents a revolutionary radiopharmaceutical for positron emission tomography imaging and opens a new era in the theranostic field.
对生理和病理过程的持续研究相应地催生了对新型放射性药物的需求,尤其是当研究因缺乏特定放射性标记靶点而受到限制时。因此,开发新型放射性示踪剂具有高度相关性,并且能够为阐明生物学重要现象的努力做出重大贡献。目前,诊疗一体化在医学和核医学领域代表着一个新的前沿领域,同一化合物可用于诊断和治疗。在人体中,铜(Cu)是含量第三丰富的金属,在许多生物学功能中发挥着关键作用。相应地,在各种后天性和遗传性病理状况下,如癌症和阿尔茨海默病,已发现铜水平发生改变。此外,多种神经退行性疾病与大脑中铜水平的升高或降低以及铜的结合或分布不当有关。在人类细胞中,膜蛋白hCtr1以能量依赖的方式结合其Cu(I)氧化态的铜。铜-64(Cu)是一种通过回旋加速器产生的放射性核素,其物理性质已显示出对诊断和/或治疗目的具有互补性。迄今为止,很少有报告描述Cu作为癌症成像放射性示踪剂的临床开发情况。在本综述中,我们重点介绍了我们对氯化铜(CuCl)作为多种肿瘤诊疗药物的理解和应用的最新见解。据我们所知,文献中未描述氯化铜有任何不良反应或临床可观察到的药理作用。因此,Cu代表了一种用于正电子发射断层扫描成像的革命性放射性药物,并开启了诊疗领域的新纪元。