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伊朗放射性药物与医用放射性同位素的生产及临床应用

Production and Clinical Applications of Radiopharmaceuticals and Medical Radioisotopes in Iran.

作者信息

Jalilian Amir Reza, Beiki Davood, Hassanzadeh-Rad Arman, Eftekhari Arash, Geramifar Parham, Eftekhari Mohammad

机构信息

Nuclear Science and Technology Research Institute, Tehran, Iran.

Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Semin Nucl Med. 2016 Jul;46(4):340-58. doi: 10.1053/j.semnuclmed.2016.01.006.

DOI:10.1053/j.semnuclmed.2016.01.006
PMID:27237443
Abstract

During past 3 decades, nuclear medicine has flourished as vibrant and independent medical specialty in Iran. Since that time, more than 200 nuclear physicians have been trained and now practicing in nearly 158 centers throughout the country. In the same period, Tc-99m generators and variety of cold kits for conventional nuclear medicine were locally produced for the first time. Local production has continued to mature in robust manner while fulfilling international standards. To meet the ever-growing demand at the national level and with international achievements in mind, work for production of other Tc-99m-based peptides such as ubiquicidin, bombesin, octreotide, and more recently a kit formulation for Tc-99m TRODAT-1 for clinical use was introduced. Other than the Tehran Research Reactor, the oldest facility active in production of medical radioisotopes, there is one commercial and three hospital-based cyclotrons currently operational in the country. I-131 has been one of the oldest radioisotope produced in Iran and traditionally used for treatment of thyrotoxicosis and differentiated thyroid carcinoma. Since 2009, (131)I-meta-iodobenzylguanidine has been locally available for diagnostic applications. Gallium-67 citrate, thallium-201 thallous chloride, and Indium-111 in the form of DTPA and Oxine are among the early cyclotron-produced tracers available in Iran for about 2 decades. Rb-81/Kr-81m generator has been available for pulmonary ventilation studies since 1996. Experimental production of PET radiopharmaceuticals began in 1998. This work has culminated with development and optimization of the high-scale production line of (18)F-FDG shortly after installation of PET/CT scanner in 2012. In the field of therapy, other than the use of old timers such as I-131 and different forms of P-32, there has been quite a significant advancement in production and application of therapeutic radiopharmaceuticals in recent years. Application of (131)I-meta-iodobenzylguanidine for treatment of neuroblastoma, pheochromocytoma, and other neuroendocrine tumors has been steadily increasing in major academic university hospitals. Also (153)Sm-EDTMP, (177)Lu-EDTMP, (90)Y-citrate, (90)Y-hydroxyapatite colloid, (188/186)Re-sulfur colloid, and (188/186)Re-HEDP have been locally developed and now routinely available for bone pain palliation and radiosynovectomy. Cu-64 has been available to the nuclear medicine community for some time. With recent reports in diagnostic and therapeutic applications of this agent especially in the field of oncology, we anticipate an expansion in production and availability. The initiation of the production line for gallium-68 generator is one of the latest exciting developments. We are proud that Iran would be joining the club of few nations with production lines for this type of generator. There are also quite a number of SPECT and PET tracers at research and preclinical stage of development preliminarily introduced for possible future clinical applications. Availability of fluorine-18 tracers and gallium-68 generators would no doubt allow rapid dissemination of PET/CT practices in various parts of our large country even far from a cyclotron facility. Also, local production and availability of therapeutic radiopharmaceuticals are going to open exciting horizons in the field of nuclear medicine therapy. Given the available manpower, local infrastructure of SPECT imaging, and rapidly growing population, the production of Tc-99m generators and cold kit would continue to flourish in Iran.

摘要

在过去三十年中,核医学在伊朗蓬勃发展,成为充满活力且独立的医学专业领域。自那时起,已有200多名核医学医师接受培训,目前在全国近158个中心执业。同一时期,首次在当地生产了锝-99m发生器以及用于传统核医学的各种冷试剂盒。当地生产在符合国际标准的同时持续稳健发展。为满足国家层面不断增长的需求并借鉴国际成果,开展了其他基于锝-99m的肽类如泛菌杀菌素、蛙皮素、奥曲肽的生产工作,最近还推出了用于临床的锝-99m TRODAT-1试剂盒配方。除了德黑兰研究堆这一生产医用放射性同位素的最古老设施外,该国目前有一台商用回旋加速器和三台医院用回旋加速器在运行。碘-131一直是伊朗生产的最古老放射性同位素之一,传统上用于治疗甲状腺毒症和分化型甲状腺癌。自2009年以来,间碘苄胍碘[131I]已在当地用于诊断应用。柠檬酸镓-67、氯化铊-201和二乙三胺五乙酸及8-羟基喹啉形式的铟-111是伊朗约二十年来早期通过回旋加速器生产的示踪剂。自1996年以来,铷-81/氪-81m发生器已用于肺通气研究。正电子发射断层显像(PET)放射性药物的实验性生产始于1998年。这项工作在2012年安装PET/CT扫描仪后不久,随着(18)F-FDG大规模生产线的开发和优化达到高潮。在治疗领域,除了使用碘-131和不同形式的磷-32等老牌药物外,近年来治疗性放射性药物的生产和应用也有了相当大的进展。间碘苄胍碘[131I]在主要学术型大学医院用于治疗神经母细胞瘤、嗜铬细胞瘤和其他神经内分泌肿瘤的应用一直在稳步增加。此外,钐[153Sm]乙二胺四甲叉膦酸、镥[177Lu]乙二胺四甲叉膦酸、钇[90Y]柠檬酸盐、钇[90Y]羟基磷灰石胶体、铼[188/186Re]硫胶体和铼[188/186Re]羟基亚乙基二膦酸盐已在当地研发出来,现在常规用于缓解骨痛和放射性滑膜切除。铜-64已在核医学领域应用了一段时间。鉴于近期有关该药物在诊断和治疗应用方面的报道,尤其是在肿瘤学领域,我们预计其生产和供应将会扩大。镓-68发生器生产线的启动是最新的一项令人振奋的进展。我们很自豪伊朗将加入拥有这种发生器生产线的少数国家行列。还有相当数量处于研究和临床前开发阶段的单光子发射计算机断层显像(SPECT)和PET示踪剂被初步引入,以备未来可能的临床应用。氟-18示踪剂和镓-68发生器的供应无疑将使PET/CT检查在我们这个大国的各个地区迅速普及,即使是远离回旋加速器设施的地方。此外,治疗性放射性药物的本地生产和供应将为核医学治疗领域开启令人兴奋的前景。鉴于现有人力、SPECT成像的本地基础设施以及快速增长的人口,锝-99m发生器和冷试剂盒的生产在伊朗将继续蓬勃发展。

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