David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
J Clin Oncol. 2012 Nov 1;30(31):3884-92. doi: 10.1200/JCO.2012.42.4887. Epub 2012 Sep 17.
Identification of cancer cell-surface biomarkers and advances in antibody engineering have led to a sharp increase in the development of therapeutic antibodies. These same advances have led to a new generation of radiolabeled antibodies and antibody fragments that can be used as cancer-specific imaging agents, allowing quantitative imaging of cell-surface protein expression in vivo. Immuno-positron emission tomography (immunoPET) imaging with intact antibodies has shown success clinically in diagnosing and staging cancer. Engineered antibody fragments, such as diabodies, minibodies, and single-chain Fv (scFv) -Fc, have been successfully employed for immunoPET imaging of cancer cell-surface biomarkers in preclinical models and are poised to bring same-day imaging into clinical development. ImmunoPET can potentially provide a noninvasive approach for obtaining target-specific information useful for titrating doses for radioimmunotherapy, for patient risk stratification and selection of targeted therapies, for evaluating response to therapy, and for predicting adverse effects, thus contributing to the ongoing development of personalized cancer treatment.
癌症细胞表面生物标志物的鉴定和抗体工程的进步,推动了治疗性抗体的快速发展。这些进步同样催生了新一代放射性标记的抗体和抗体片段,可作为癌症特异性成像剂,从而实现细胞表面蛋白表达的定量体内成像。完整抗体的免疫正电子发射断层扫描(immunoPET)成像在癌症的诊断和分期方面已在临床上取得成功。工程化抗体片段,如二抗体、迷你抗体和单链 Fv(scFv)-Fc,已成功应用于癌症细胞表面生物标志物的 immunoPET 成像的临床前模型,有望将当日成像引入临床开发。免疫 PET 成像有可能为放射性免疫治疗的剂量滴定、患者风险分层和靶向治疗的选择、治疗反应的评估以及不良反应的预测提供一种非侵入性的方法,从而有助于个性化癌症治疗的不断发展。