TY - JOUR T1 - <strong>Radioimmunotherapy in Oncology</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 2700 LP - 2700 VL - 63 IS - supplement 2 AU - Sara Harsini AU - Thomas Werner AU - Mona-Elisabeth Revheim AU - Abass Alavi AU - Babak Saboury Y1 - 2022/06/01 UR - http://jnm.snmjournals.org/content/63/supplement_2/2700.abstract N2 - 2700 Introduction: To provide an overview on the potential clinical benefit and limitations of radioimmunotherapy (RIT) in the treatment of hematological malignancies and solid tumors.Methods: The specific irradiation of antigens expressed on the tumor surface with selective radiolabeled antibodies, or radioimmunotherapy, constitutes an attractive therapeutic approach. RIT has been an active field of research spanning more than 30 years, in both molecular biology to recognize pertinent targets and to select corresponding monoclonal antibodies (mAbs) and in chemistry to radiolabel mAbs. The putative benefit of RIT lies in selective targeting of antigens on cancer cells using mAbs, to deliver damaging radiation. Despite the first successes of radiolabeled mAbs in hematological malignancies with the anti-CD20 mAbs [131I]I-Tositumomab (Bexxar) and [90Y]Y-Ibritumomab tiuxetan (Zevalin), either in combination strategies or as first-line treatment, these strategies are not widely used since other therapeutic options were deemed more influential on patient survival and could be easier to implement on-site than radiopharmaceuticals. Multiple factors including concerns about radiation toxicity, availability, and the development of competing therapeutic options can explain the limited use of these radiopharmaceuticals in clinical practice. Nonetheless, the introduction of a diversity of new targets, the success of newly validated immunoconjugates, the development of novel labeling methods with potent radionuclides including α-emitters as well as the implementation of new treatment strategies to improve RIT are all in favor of wider use of radiopharmaceuticals in clinical practice for cancer RIT.Results: Different approaches addressing RIT limitations for both hematological malignancies and solid tumors have been studied, some aiming at further enhancing the efficacy of RIT on the tumor cells, and some aiming at diminishing toxicity to normal tissues. These recent developments include but are not limited to combination regimens, locoregional approaches, pre-targeting, mAb fragments, and imaging and dosimetry prior to RIT. In combination regimens, RIT can be combined with other therapeutic strategies such as chemotherapeutic drugs, radiotherapy, physical methods such as hyperthermia or pulsed high intensity focused ultrasound, chemical methods to further enhance the internalization of the radiolabeled mAb using cell-penetrating peptides or vasoactive agents, inhibitors of poly(ADP-ribose) polymerases (PARP), traditional immunotherapy, checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1), its ligand programmed death-ligand 1 (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), oncolytic viruses, or chimeric antigen receptor T cells (CAR T cells). Locoregional approaches involve local administration of radiolabeled mAb to improve targeting and decrease toxicity as compared to systemic delivery. In pre-targeting strategy, we separate the injection of the mAb and the therapeutic radionuclide into two steps by first injecting nonradioactive mAb allowing for tumor accumulation and slow clearance of the unbound mAb from the blood and then injecting a radioactive small molecule that binds with the tumor-bound mAb in the second step, to achieve the same or even greater targeting performance as that of peptidomimetics and small molecules used in targeted radionuclide therapy. Using mAb fragments such as enzymatically cleaved mAb fragments (F(ab′)2, F(ab′), Fab), genetically engineered protein scaffolds such as minibodies, diabodies or single-chain variable fragments (scFv), and smaller molecules like nanobodies or affibodies, can theoretically result in increased blood clearance of the radioimmunoconjugate and thus reduced hematological toxicity. Moreover, imaging and dosimetry prior to RIT can improve the prediction of the safety and effectiveness of radiopharmaceuticals.Conclusions: This educational exhibit will elaborate on the principles of RIT, main achievements, and recent developments that address RIT limitations in both hematological malignancies and solid tumors. ER -