Barbet Jacques, Bardiès Manuel, Bourgeois Mickael, Chatal Jean-François, Chérel Michel, Davodeau François, Faivre-Chauvet Alain, Gestin Jean-François, Kraeber-Bodéré Françoise
Centre de Recherche en Cancérologie de Nantes-Angers, Inserm, Université de Nantes, Nantes, France.
Methods Mol Biol. 2012;907:681-97. doi: 10.1007/978-1-61779-974-7_38.
Radiolabeled antibodies were studied first for tumor detection by single-photon imaging, but FDG PET stopped these developments. In the meantime, radiolabeled antibodies were shown to be effective in the treatment of lymphoma. Radiolabeling techniques are well established and radiolabeled antibodies are a clinical and commercial reality that deserves further studies to advance their application in earlier phase of the diseases and to test combination and adjuvant therapies including radiolabeled antibodies in hematological diseases. In solid tumors, more resistant to radiations and less accessible to large molecules such as antibodies, clinical efficacy remains limited. However, radiolabeled antibodies used in minimal or small-size metastatic disease have shown promising clinical efficacy. In the adjuvant setting, ongoing clinical trials show impressive increase in survival in otherwise unmanageable tumors. New technologies are being developed over the years: recombinant antibodies and pretargeting approaches have shown potential in increasing the therapeutic index of radiolabeled antibodies. In several cases, clinical trials have confirmed preclinical studies. Finally, new radionuclides, such as lutetium-177, with better physical properties will further improve the safety of radioimmunotherapy. Alpha particle and Auger electron emitters offer the theoretical possibility to kill isolated tumor cells and microscopic clusters of tumor cells, opening the perspective of killing the last tumor cell, which is the ultimate challenge in cancer therapy. Preliminary preclinical and preliminary clinical results confirm the feasibility of this approach.
放射性标记抗体最初是通过单光子成像用于肿瘤检测研究的,但氟代脱氧葡萄糖正电子发射断层扫描(FDG PET)阻止了这些研究的进展。与此同时,放射性标记抗体在淋巴瘤治疗中显示出有效性。放射性标记技术已经成熟,放射性标记抗体已成为临床和商业现实,值得进一步研究以推动其在疾病早期阶段的应用,并测试包括放射性标记抗体在内的血液系统疾病的联合和辅助治疗方法。在实体瘤中,由于对辐射更具抗性且对抗体等大分子的摄取较少,临床疗效仍然有限。然而,用于微小或小尺寸转移性疾病的放射性标记抗体已显示出有前景的临床疗效。在辅助治疗方面,正在进行的临床试验表明,在其他难以治疗的肿瘤中,生存率有显著提高。多年来一直在开发新技术:重组抗体和预靶向方法在提高放射性标记抗体的治疗指数方面已显示出潜力。在一些情况下,临床试验证实了临床前研究的结果。最后,具有更好物理性质的新放射性核素,如镥 - 177,将进一步提高放射免疫治疗的安全性。α粒子和俄歇电子发射体提供了杀死孤立肿瘤细胞和微小肿瘤细胞簇的理论可能性,开启了杀死最后一个肿瘤细胞的前景,这是癌症治疗中的最终挑战。初步临床前和初步临床结果证实了这种方法的可行性。