New Advances in Radioimmunotherapy for the Treatment of Cancers

Radioimmunotherapy (RIT) has been in use for more than 20 years and has progressed significantly with the discovery of new molecular targets, the development of new stable chelates, the humanization of monoclonal antibodies (mAbs), and the use of pretargeting techniques. Today, two products targeting the CD20 antigen are approved in the treatment of B cell lymphoma: 131I-tositumomab (Bexxar®) and 90Y-ibritumomab tiuxetan (Zevalin®). RIT can be integrated in clinical practice for treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy in frontline treatment in FL patients. High-dose treatment, RIT as consolidation, RIT in first-line treatment, fractionated RIT, and use of new humanized mAbs, in particular targeting CD22, showed promising results in B cell lymphoma. In other hemopathies, such as multiple myeloma, efficacy has been demonstrated in preclinical studies. In solid tumors, more resistant to radiations and less accessible to large molecules such as mAbs, clinical efficacy remains limited. However, RIT used in minimal or small-size metastatic disease has shown promising clinical efficacy. Pretargeting approaches have been potential in increasing the therapeutic index of radiolabeled antibodies. Finally, new beta emitters such as lutetium-177 with better physical properties will further improve the safety of RIT. Moreover, alpha emitters such as bismuth-213 or astatine-211 offer the theoretical possibility to eradicate the last microscopic clusters of tumor cells, in the setting of consolidation. Personalized dosimetry protocols, particularly based on quantitative positron emission tomography (PET) imaging, should be developed to optimize injected activity.