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 of 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 they 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; leucine is an exception because it is quantitatively incorporated into proteins. The functions of these natural amino acid imaging agents are based on amino acid transport and protein incorporation. Lee et al. (8) synthesized a series of In-labeled alanine and lysine derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), DO3A, and DO2A. Based on their cellular accumulation in tumor cells, In-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid-l-homoalanine (In-DO3A-H) was selected for use with single-photon emission computed tomography (SPECT) imaging studies in tumor-bearing nude mice.
人们已经研究了多种碳（C）和氟（F）标记的氨基酸在正电子发射断层扫描（PET）肿瘤学中的潜在用途（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）。这些氨基酸由天然存在的氨基酸组成，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）。由于它们的代谢活性，包括掺入蛋白质中，其代谢活性高于大多数正常细胞，所以它们被保留在肿瘤细胞中（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），但它们未获得美国食品药品监督管理局的批准。这些试剂通过各种氨基酸转运体进入细胞并掺入蛋白质中。与细胞摄取的总量相比，掺入蛋白质中的放射性标记氨基酸的比例通常较小；亮氨酸是个例外，因为它能定量地掺入蛋白质中。这些天然氨基酸成像剂的功能基于氨基酸转运和蛋白质掺入。Lee等人（8）合成了一系列1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）、DO3A和DO2A的铟（In）标记的丙氨酸和赖氨酸衍生物。基于它们在肿瘤细胞中的细胞积累情况，1,4,7,10-四氮杂环十二烷-1,4,7-三乙酸-L-高丙氨酸铟（In-DO3A-H）被选用于荷瘤裸鼠的单光子发射计算机断层扫描（SPECT）成像研究。
