Larson S M
Department of Medical Imaging, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer. 1991 Feb 15;67(4 Suppl):1253-60. doi: 10.1002/1097-0142(19910215)67:4+<1253::aid-cncr2820671523>3.0.co;2-j.
Targeting of radioactivity to tumors using antitumor antibodies is evolving from a laboratory curiosity toward a practical diagnostic and therapeutic technique that promises widespread benefits for many common human cancers. The development of the hybridoma technique by Kohler and Milstein for producing monoclonal antibodies is probably the single most important contribution to the development of this field. A large array of monoclonal antibodies against many human tumors have been created and labeled with a variety of radioisotopes; 110 clinical trials have been identified from the literature between the interval of 1978 to the present. These studies are beginning to form the basis for certain conclusions regarding likely benefits for certain combinations of antitumor antibodies and isotopes in specific instances of clinical management in patients with malignant neoplasms. For example, in melanoma, lymphoma, neuroblastoma, and colorectal malignancies, radiolabeled antibodies have demonstrated occult tumors, which could not be disclosed with conventional methodologies. Radioimmunotherapy of malignant lymphoma is achieving durable remissions in patients who have failed conventional forms of therapy. For the most part, these advances have been achieved through intelligent application of known principles of immunochemistry, imaging physics, and tumor immunology. Progress has been slow but steady. In a few instances, the term "magic bullet" is warranted in describing the targeting of a particular radiolabeled antibody to a human tumor. I-131, 3-F8, an IgG3 against the GD2 antigen of neuroblastoma, which was introduced by Cheung, and In-111 T-101, against the CD5 antigen of T-cells, which was developed by Royston, stand out because of the consistency and high concentration of radioactive targeting to human tumors in clinical trials. If certain technical innovations fulfill their initial promise, the future will be bright for radioimmunologic methods of diagnosis and therapy. Genetic engineering will permit the development of "humanized" antibodies with biologic properties that favor tumor localization. New chemical approaches will broaden the range of isotopes available as diagnostic and therapeutic radiolabels. Application of modern imaging methodologies, such as positron emission tomography (PET), will detect more lesions of smaller size and permit quantitative imaging for dosimetry considerations. Greater speed and ease of use of computerized work stations will lead to the broader application of fusion imaging in which radioantibody images will be viewed simultaneously with TCT or MRI for better anatomic correlation of abnormal sites of antigen-reactive tumor deposits.
利用抗肿瘤抗体将放射性物质靶向肿瘤，正从实验室的新奇事物发展成为一种实用的诊断和治疗技术，有望为许多常见人类癌症带来广泛益处。科勒和米尔斯坦发明的用于生产单克隆抗体的杂交瘤技术，可能是对该领域发展最重要的一项贡献。现已制备出大量针对多种人类肿瘤的单克隆抗体，并标记了各种放射性同位素；从1978年至今的文献中已确定了110项临床试验。这些研究开始为某些结论奠定基础，即关于在恶性肿瘤患者的特定临床管理实例中，某些抗肿瘤抗体与同位素组合可能带来的益处。例如，在黑色素瘤、淋巴瘤、神经母细胞瘤和结直肠癌中，放射性标记抗体已显示出隐匿性肿瘤，而这些肿瘤用传统方法无法检测到。恶性淋巴瘤的放射免疫疗法正在使那些传统治疗方法无效的患者实现持久缓解。在很大程度上，这些进展是通过明智地应用免疫化学、成像物理学和肿瘤免疫学的已知原理取得的。进展虽缓慢但稳定。在某些情况下，用“神奇子弹”一词来描述特定放射性标记抗体对人类肿瘤的靶向作用是恰当的。I-131、3-F8（一种由张发明的针对神经母细胞瘤GD2抗原的IgG3）以及In-111 T-101（一种由罗伊斯顿开发的针对T细胞CD5抗原的抗体）脱颖而出，因为在临床试验中它们对人类肿瘤的放射性靶向具有一致性且浓度高。如果某些技术创新能实现其最初的承诺，放射免疫诊断和治疗方法的未来将一片光明。基因工程将使具有有利于肿瘤定位生物学特性的“人源化”抗体得以开发。新的化学方法将拓宽可作为诊断和治疗放射性标记的同位素范围。应用现代成像方法，如正电子发射断层扫描（PET），将能检测到更多更小的病灶，并可进行定量成像以考虑剂量测定。计算机工作站更快的速度和更便捷的使用将导致融合成像得到更广泛的应用，在融合成像中，放射性抗体图像将与TCT或MRI同时查看，以便更好地对抗原反应性肿瘤沉积的异常部位进行解剖学关联。
