Leung Kam
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
A variety of C- and F-labeled amino acids have been studied for potential use in positron emission tomography (PET) oncology (1, 2). Most brain tumors show an increased uptake of amino acids as compared with normal brain tissues (3). These amino acids are composed of naturally occurring amino acids, such as L-[C]leucine, -[C]methyl-L-methionine ([C]MET), and L-[C]tyrosine, and non-natural amino acids, such as [C]aminoisobutyric acid, [C]1-aminocyclopentane-1-carboxylic acid, and [C]1-aminocyclobutane-1-carboxylic acid. I-Labeled amino acids are also used in oncological imaging (1, 4, 5). Some 20 amino acid transporter systems have been identified (1). Most amino acids are taken up by tumor cells through an energy-independent L-type amino acid transporter system, a Na-dependent transporter system A, or a Na-dependent system B (6). They are retained in tumor cells due to their metabolic activities, including incorporation into proteins, which are higher than most normal cells (1). Malignant transformation increases the use of amino acids for energy, protein synthesis, and cell division. Tumor cells have been found to have overexpressed transporter systems (7). L-[C]MET, [F]fluorotyrosine, L-[C]leucine, and [F]fluoro-α-methyl tyrosine have been widely used in the detection of tumors (2, 6) but are not approved by the United States Food and Drug Administration. These agents are moved into cells by various amino acid transporters and are incorporated into proteins. The fraction of radiolabeled amino acid that is incorporated into protein is usually small compared to the total amount taken up into the cell except for leucine which is quantitatively incorporated into proteins. These natural amino acid images are based on amino acid transport and protein incorporation. [C]MET has been widely used in the detection of brain, head and neck, lung, and breast cancers as well as lymphomas (2) [PubMed]. [C]MET can cross the blood–brain barrier, and while it is incorporated mainly into proteins, but [C]MET is also incorporated into lipid, RNA, and DNA. [C]MET PET imaging is more sensitive to radiotherapy compared to [F]FDG and is useful for monitoring treatment of cancer. -[C]Methyl-L-cysteine ([C]MCYS), an analog of [C]MET, was evaluated as a PET tumor imaging agent (8).
人们已经对多种碳（C）和氟（F）标记的氨基酸进行了研究，以探讨其在正电子发射断层扫描（PET）肿瘤学中的潜在应用（1,2）。与正常脑组织相比，大多数脑肿瘤对氨基酸的摄取增加（3）。这些氨基酸包括天然存在的氨基酸，如L-[碳-11]亮氨酸、O-[碳-11]甲基-L-蛋氨酸（[碳-11]MET）和L-[碳-11]酪氨酸，以及非天然氨基酸，如[碳-11]氨基异丁酸、[碳-11]1-氨基环戊烷-1-羧酸和[碳-11]1-氨基环丁烷-1-羧酸。碘（I）标记的氨基酸也用于肿瘤成像（1,4,5）。已鉴定出约20种氨基酸转运系统（1）。大多数氨基酸通过能量非依赖型L型氨基酸转运系统、钠依赖型转运系统A或钠依赖型系统B被肿瘤细胞摄取（6）。由于其代谢活性，包括掺入蛋白质，它们被保留在肿瘤细胞中（蛋白质掺入量高于大多数正常细胞）（1）。恶性转化增加了氨基酸用于能量、蛋白质合成和细胞分裂的量。已发现肿瘤细胞中转运系统过表达（7）。L-[碳-11]MET、[氟-18]氟酪氨酸、L-[碳-11]亮氨酸和[氟-18]氟-α-甲基酪氨酸已广泛用于肿瘤检测（2,6），但未获得美国食品药品监督管理局的批准。这些药物通过各种氨基酸转运体进入细胞并掺入蛋白质。与细胞摄取的总量相比，掺入蛋白质的放射性标记氨基酸的比例通常较小，但亮氨酸除外，亮氨酸可定量掺入蛋白质。这些天然氨基酸图像基于氨基酸转运和蛋白质掺入。[碳-11]MET已广泛用于脑、头颈、肺和乳腺癌以及淋巴瘤的检测（2）[PubMed]。[碳-11]MET可以穿过血脑屏障，虽然它主要掺入蛋白质，但也掺入脂质、RNA和DNA。与[氟-18]FDG相比，[碳-11]MET PET成像对放疗更敏感，可用于监测癌症治疗。O-[碳-11]甲基-L-半胱氨酸（[碳-11]MCYS），[碳-11]MET的类似物，被评估为一种PET肿瘤成像剂（8）。
