Vallabhajosula Shankar
Division of Nuclear Medicine, Department of Radiology,New York Presbyterian Hospital, Cornell University, New York, NY 10021, USA.
Semin Nucl Med. 2007 Nov;37(6):400-19. doi: 10.1053/j.semnuclmed.2007.08.004.
Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on regulatory compliance in addition to documentation of potential safety and efficacy by various investigators.
分子成像是在活体系统中对分子和细胞水平的生物过程进行可视化、特征描述和测量。目前,正电子发射断层扫描/计算机断层扫描(PET/CT)是医学成像领域发展最为迅速的领域之一,在癌症患者的临床管理中有许多应用。尽管[18F]氟脱氧葡萄糖(FDG)-PET/CT成像在几种癌症中具有高特异性和敏感性且有诸多应用,但必须认识到FDG并非用于成像恶性疾病的“特异性”放射性示踪剂。高度“肿瘤特异性”和“肿瘤细胞信号特异性”的PET放射性药物对于满足基于放射性同位素的分子成像技术不断增长的需求至关重要。在过去15年中,许多替代性PET示踪剂已在临床前和临床研究中被提出并评估以更恰当地表征肿瘤生物学特性。本期有几位研究人员正在综述几种18F标记的放射性示踪剂(如氟化物、FDOPA、FLT、FMISO、FES和FCH)的潜在临床应用价值。本文将概述18F标记的PET放射性药物的设计与开发、放射化学以及放射性示踪剂在肿瘤细胞摄取和定位的机制。2000年,美国食品药品监督管理局基于文献综述批准了FDG-PET的临床适应症,这是PET迅速融入核医学实践(尤其是肿瘤学领域)的一项重大突破。放射性药物的批准通常要求制造商或公司提交一份“新药申请”,清晰记录药物的两个主要方面:(1)按照现行良好生产规范生产PET药物;(2)药物在特定适应症下的安全性和有效性。18F标记的PET放射性药物的潜在常规临床应用价值除了需要各研究人员证明其潜在安全性和有效性外,还取决于是否符合监管要求。