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PET显像已广泛应用于肿瘤诊断、鉴别诊断、分期、疗效评价以及预后监测,与常规的影像学方法比较,具有明显的优势。与特异性更强的受体显像相比,PET代谢显像不是反映单一靶分子表达的单靶点分子显像,而是反映肿瘤代谢过程中涉及的多个转运体和酶的多靶点显像,更有利于提高对肿瘤探测的灵敏度[1]。利用肿瘤代谢异常增高的特点,PET可对肿瘤进行糖代谢、脂类代谢、核酸代谢和氨基酸代谢显像。18F-FDG是目前临床应用最广泛的一种PET糖代谢显像剂,但18F-FDG PET显像容易出现一些假阳性或假阴性[2-3]。脂肪酸代谢显像在脂类代谢PET显像中占有非常重要的地位,可弥补糖代谢、氨基酸代谢的某些不足[4]。
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脂肪酸不但是构成生物膜脂质和信号分子的必需组成成分,也是心肌和肿瘤细胞重要的能量代谢底物。对于绝大多数恶性肿瘤来说,为了维持肿瘤细胞的快速增殖,肿瘤细胞除了糖酵解活性增强以外,脂肪酸代谢也会增强,特别是某些糖代谢率较低的恶性肿瘤,脂肪酸代谢率反而会升高,脂肪酸代谢可以有效弥补糖代谢的不足[1-2]。脂肪酸代谢包括分解代谢和合成代谢,长链脂肪酸作为能量底物主要参与分解代谢,利用长链脂肪酸β-氧化提供的能量可对心肌进行显像。短链脂肪酸如乙酸、丙酸等,除参与脂肪酸分解代谢外,还可能参与脂肪酸从头合成途径,从短链脂肪酸聚合成长链脂肪酸[3]。参与脂肪酸合成的关键酶较多,最为重要的是乙酰辅酶A合成酶(acetyl-coA synthetase,ACSS)、乙酰辅酶A羧化酶(acetyl-coA carboxylase,ACC)和脂肪酸合成酶(fatty acid synthetase,FASN)[5-6]。研究发现脂肪酸合成和氧化代谢相关的重要酶类,如FASN、ACC、ACSS等在肿瘤组织中过度高表达,而在正常组织中不表达或低表达[5-10]。因此,利用靶向FASN、ACC、ACSS的标记短链脂肪酸,可实现肿瘤脂肪酸代谢显像(表 1)。
类型 PET显像剂 分子式 应用 乙酸类 11C-AC 肝癌、肾癌、前列腺癌、膀胱癌、脑肿瘤、头颈部等肿瘤的诊断和鉴别诊断 18F-FAC 肝癌、肾癌、前列腺癌等肿瘤的诊断和鉴别诊断 丙酸类 18F-FPA 前列腺癌、乳腺癌等的临床前研究 特戊酸类 18F-FPIA 前列腺癌、乳腺癌等的临床前研究 注:表中,AC:乙酸盐;FAC:氟代乙酸盐;FPA:氟代丙酸;FPIA:氟代特戊酸。 表 1 常用短链脂肪酸PET显像剂
Table 1. PET tracers of short-chain fatty acids
肿瘤短链脂肪酸代谢PET显像剂研究进展
Progress on short-chain fatty acid tumor molecular probes for PET imaging
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摘要: 18F-FDG PET显像在临床上发挥着越来越重要的作用,但其在某些肿瘤的应用中存在一定的弊端,易产生假阳性和假阴性。脂肪酸代谢PET显像在脂类代谢显像中占有非常重要的地位,在一定程度上可弥补糖代谢的不足,能提高对肿瘤诊断的灵敏度和准确率。笔者就目前应用于临床前和临床研究中的肿瘤短链脂肪酸代谢PET显像剂进行综述。
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关键词:
- 短链脂肪酸 /
- 诊断 /
- 分子探针 /
- 正电子发射断层显像术
Abstract: 18F-FDG PET plays an increasingly important role in clinical assessment. However, some false-positive and false-negative results for certain tumors have been achieved with 18F-FDG. Furthermore, fatty acid metabolic imaging is valuable in lipid-metabolism PET imaging. This technique compensates for the deficiency of 18F-FDG PET examination and improves the diagnostic sensitivity and accuracy of tumor detection. This review provides an overview of recent developments in the use of short-chain fatty acid radioactive probes in PET imaging.-
Key words:
- Short-chain fatty acid /
- Diagnosis /
- Molecular probes /
- Positron-emission tomography
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表 1 常用短链脂肪酸PET显像剂
Table 1. PET tracers of short-chain fatty acids
类型 PET显像剂 分子式 应用 乙酸类 11C-AC 肝癌、肾癌、前列腺癌、膀胱癌、脑肿瘤、头颈部等肿瘤的诊断和鉴别诊断 18F-FAC 肝癌、肾癌、前列腺癌等肿瘤的诊断和鉴别诊断 丙酸类 18F-FPA 前列腺癌、乳腺癌等的临床前研究 特戊酸类 18F-FPIA 前列腺癌、乳腺癌等的临床前研究 注:表中,AC:乙酸盐;FAC:氟代乙酸盐;FPA:氟代丙酸;FPIA:氟代特戊酸。 -
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