Gulyás B, Halldin C
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Q J Nucl Med Mol Imaging. 2012 Apr;56(2):173-90.
Brain tumors have a relatively high incidence (>14/100000 people/year) and represent a major cause of death in the population. The direct and indirect costs of brain tumors are high in the developed countries (5.2 bn EUR/year in the EU; 4.46 bn USD/year in the US). A combination of recent advancements in molecular neuroimaging, with positron emission tomography (PET) in the first place, providing clinicians with an improved diagnostic and therapy follow-up efficacy, novel approaches in the field of neurosurgery (including neuronavigation, intraoperative control of the nervous function, tumor histology and volume), and developments in treatment strategies (including new chemotherapeutics and new targeted agents, immunotherapies, sophisticated irradiation protocols) has in the past years improved the survival of brain tumor patients. A major component of further improvements is related to advancements in the development of novel molecular imaging biomarkers for brain tumor detection, including new PET radiopharmacons with high specificity, sensitivity and diagnostic accuracy. Despite the fact that FDG is the "working horse" of brain tumor imaging with PET and well over 90 % of diagnostic imaging studies in neuro-oncology are made with FDG world-wide, due to its sub-optimal specificity and sensitivity the search for non-FDG brain tumor PET radiotracers has been intensifying during the past decade in order to improve the diagnostic sensitivity, specificity and accuracy of molecular imaging of brain tumors. The most promising non-FDG brain tumor radiotracers include radioactively labeled nucleoside and amino acid analogues, tracers of oxidative metabolism, fatty acid metabolism and hypoxia, as well as receptor ligands of various kinds. The most widely tested non-FDG radiotracers include [11C]methionine (MET), [18F]fluorothymidine (FLT), [18F]fluoroethyl-l-tyrosine (FET), [18F]fluoro-α-methyltyrosine (FMT), [18F]fluoromisonidazole (F-MISO), 6-[18F]fluoro-dihydroxy-l-phenylalanine (F-DOPA), [11C]choline (CHO) and [18F]choline. The selective advantages of these radiotracers, compared to FDG, are varying, MET and FET appearing to be the most useful dedicated glioma radiotracers. Nevertheless, several other non-metabolic radiopharmaceuticals are also being tested or are in the validation phase. Although novel dedicated radiotracer candidates should offer an increased selectivity, specificity and diagnostic accuracy when compared to the recently existing brain tumor tracers, a dual or a multitracer approach may still offer the optimal solution in brain tumor imaging with PET in the near future.
脑肿瘤发病率相对较高（>14/100000人/年），是人群中的主要死因。在发达国家，脑肿瘤的直接和间接成本很高（欧盟每年52亿欧元；美国每年44.6亿美元）。近年来，分子神经影像学取得了一系列进展，首先是正电子发射断层扫描（PET），为临床医生提供了更高的诊断和治疗随访效果；神经外科领域也出现了新方法（包括神经导航、术中神经功能控制、肿瘤组织学和体积测定）；治疗策略也有所发展（包括新的化疗药物和新的靶向药物、免疫疗法、精密放疗方案），这些在过去几年中提高了脑肿瘤患者的生存率。进一步改善的一个主要因素与新型分子成像生物标志物的开发进展有关，这些标志物用于脑肿瘤检测，包括具有高特异性、敏感性和诊断准确性的新型PET放射性药物。尽管氟代脱氧葡萄糖（FDG）是PET脑肿瘤成像的“主力军”，全球超过90%的神经肿瘤诊断成像研究都使用FDG，但由于其特异性和敏感性欠佳，在过去十年中，人们一直在加紧寻找非FDG脑肿瘤PET放射性示踪剂，以提高脑肿瘤分子成像的诊断敏感性、特异性和准确性。最有前景的非FDG脑肿瘤放射性示踪剂包括放射性标记的核苷和氨基酸类似物、氧化代谢示踪剂、脂肪酸代谢和缺氧示踪剂，以及各种受体配体。测试最广泛的非FDG放射性示踪剂包括[11C]蛋氨酸（MET）、[18F]氟胸苷（FLT）、[18F]氟乙基-L-酪氨酸（FET）、[18F]氟-α-甲基酪氨酸（FMT）、[18F]氟米索硝唑（F-MISO）、6-[18F]氟二羟基-L-苯丙氨酸（F-DOPA）、[11C]胆碱（CHO）和[18F]胆碱。与FDG相比，这些放射性示踪剂的选择性优势各不相同，MET和FET似乎是最有用的专用胶质瘤放射性示踪剂。然而，其他几种非代谢性放射性药物也在测试或处于验证阶段。尽管与现有的脑肿瘤示踪剂相比，新型专用放射性示踪剂候选物应具有更高的选择性、特异性和诊断准确性，但在不久的将来，双示踪剂或多示踪剂方法可能仍会为PET脑肿瘤成像提供最佳解决方案。
