Leung Kam
National for Biotechnology Information, NLM, NIH, Bethesda, MD
Carcinoembryonic antigen (CEA) was first identified from extracts of human colon adenocarcinoma (1) and fetal gut (2). It is a β-glycoprotein, and its predominant expression on the cell surface is increased in a variety of carcinomas and in certain inflammatory states such as inflammatory bowel disease (3, 4). CEA has a molecular weight of ~180 kDa, and it can be shed and detected in the serum (5). CEA expression is observed in patients with various carcinomas of the colon, lungs, thyroid, uterus, ovaries, pancreas, and medullary thyroid (6). Radiolabeled monoclonal antibodies (mAbs) have been developed for both the diagnosis and treatment of tumors (7, 8). Tc-Arcitumomab (a murine anti-CEA mAbFab’ fragment) was approved by the United States Food and Drug Administration in 1999 for whole-body planar and single-photon emission computed tomography (SPECT) imaging of CEA expression. Single-chain variable fragments (scFvs) of antibodies with a molecular mass of 25 kDa are cleared very rapidly from the circulation, but they exhibit poor tumor retention because they have lower affinity than the parent antibody (9). On the other hand, bivalent antibody fragments possess more ideal tumor-targeting characteristics, including rapid tissue penetration, high target retention, and rapid blood clearance. The diabody fragment (a dimer of scFvs; molecular mass = 55 kDa) has been evaluated for targeting in several tumor antigen systems and has demonstrated rapid tumor localization and high-contrast imaging (9, 10). In particular, a murine anti-CEA T84.66 diabody, which retains excellent CEA-binding properties, was radiolabeled with I for localization of CEA-positive tumors in mice (11). However, for clinical development, F offers the advantages of easy availability, a higher positron yield (nearly 100% 23% for I), and a short half-life (109.7 min 4.18 days for I). Therefore, a diabody labeled with F is more suitable for routine clinical use because of the biological targeting and clearance kinetics of diabodies. 4-[F]Fluorobenzoyl-T84.66 diabody ([F]FB-T84.66 diabody) is being developed as a positron emission tomography (PET) agent to image CEA-expressing tumors.
癌胚抗原（CEA）最初是从人结肠腺癌提取物（1）和胎儿肠道提取物（2）中鉴定出来的。它是一种β-糖蛋白，在多种癌症以及某些炎症状态（如炎症性肠病）中，其在细胞表面的主要表达会增加（3,4）。CEA的分子量约为180 kDa，它可以脱落并在血清中被检测到（5）。在患有结肠、肺、甲状腺、子宫、卵巢、胰腺和甲状腺髓样癌等各种癌症的患者中可观察到CEA表达（6）。已开发出放射性标记的单克隆抗体（mAb）用于肿瘤的诊断和治疗（7,8）。锝标记的阿西妥单抗（一种鼠抗CEA mAbFab’片段）于1999年被美国食品药品监督管理局批准用于CEA表达的全身平面和单光子发射计算机断层扫描（SPECT）成像。分子量为25 kDa的抗体单链可变片段（scFv）从循环中清除非常迅速，但由于其亲和力低于亲本抗体，所以在肿瘤中的滞留性较差（9）。另一方面，二价抗体片段具有更理想的肿瘤靶向特性，包括快速组织穿透、高靶点滞留和快速血液清除。双特异性抗体片段（scFv的二聚体；分子量 = 55 kDa）已在多种肿瘤抗原系统中进行了靶向评估，并已证明具有快速肿瘤定位和高对比度成像（9,10）。特别是，一种保留了优异CEA结合特性的鼠抗CEA T84.66双特异性抗体用碘进行放射性标记，用于小鼠体内CEA阳性肿瘤的定位（11）。然而，对于临床开发，氟具有易于获得、较高的正电子产率（碘为近100% 对23%）和较短的半衰期（氟为109.7分钟 对碘为4.18天）等优点。因此，由于双特异性抗体的生物靶向和清除动力学，用氟标记的双特异性抗体更适合常规临床使用。4-[氟]氟苯甲酰-T84.66双特异性抗体（[氟]FB-T84.66双特异性抗体）正在被开发为一种正电子发射断层扫描（PET）剂，用于对表达CEA的肿瘤进行成像。
