Kitson Sean L, Cuccurullo Vincenzo, Moody Thomas S, Mansi Luigi
Department of Biocatalysis and Isotope Chemistry, Almac, 20 Seagoe Industrial Estate, Craigavon, BT63 5QD, United Kingdom.
Curr Radiopharm. 2013 Jun 6;6(2):57-71. doi: 10.2174/1874471011306020001.
Targeted alpha therapy (TAT) is an investigational procedure which utilises monoclonal antibodies (mAbs), peptide conjugates and/or other chemical compounds. These bio-vectors are able to transport a dose of alpha particles to destroy cancer cells. Radionuclide antibody-conjugates (RACs), labelled with beta emitters, have already been used in humans. More recently, TAT has been introduced to treat oncological diseases mainly leukaemia and lymphoma. Encouraging results have also been obtained in solid neoplasms with the administration of anti-tenascin. This chimeric antibody labelled with astatine-211 was delivered in patients with recurrent brain tumours into a surgically created cavity. Conversely, a clinical trial using a standard TAT approach to treat patients with metastatic melanoma, observed the shrinkage of the solid tumour mass. This response in melanoma may lead to an alternative mechanism for TAT, called tumour-antivascular- alpha-therapy (TAVAT), and forms the basis of a novel approach to the treatment of cancer disease states. In this paper, we will concentrate mainly on the application of TAT using antibodies. In particular, an investigation into the major general features connected with the use of alpha emitters in cancer therapy will be discussed. The prospective role of TAT with RACs will also be outlined briefly, especially focussing on the most important therapeutic strategies to date based on antibodies radiolabelled with beta emitters.
靶向α治疗(TAT)是一种研究性程序,它利用单克隆抗体(mAb)、肽偶联物和/或其他化合物。这些生物载体能够携带一定剂量的α粒子来摧毁癌细胞。已标记β发射体的放射性核素抗体偶联物(RAC)已用于人体。最近,TAT已被引入用于治疗肿瘤疾病,主要是白血病和淋巴瘤。在实体瘤中给予抗腱生蛋白也取得了令人鼓舞的结果。这种用砹-211标记的嵌合抗体被注射到复发性脑肿瘤患者手术创建的腔隙中。相反,一项使用标准TAT方法治疗转移性黑色素瘤患者的临床试验观察到实体瘤肿块缩小。黑色素瘤中的这种反应可能导致TAT的另一种机制,称为肿瘤抗血管α治疗(TAVAT),并构成一种治疗癌症疾病状态新方法的基础。在本文中,我们将主要关注使用抗体的TAT的应用。特别是,将讨论对与在癌症治疗中使用α发射体相关的主要一般特征的研究。还将简要概述TAT与RAC的潜在作用,尤其关注基于标记有β发射体的抗体的最重要治疗策略。