**3. The concept of therapy**

Various alpha- and beta-radiation-emitting isotopes for therapy are mostly labeled with peptides or antibodies for specific tumor targeting, which are used only as vehicles to deliver ionizing radiation to the tumor tissue. The vehicle concentrates radioactivity at the tumor tissue expressing specific tissue elements and avoiding concentrating at normal cells [2, 7, 10]. Different radioligands are being developed and investigated for uniquely targeting molecular receptors or intracellular components that currently lead to planning personal patient-tailored therapy [43]. Radionuclides are coupled to ligands that recognize and bind the tumor-associated molecules, ensuring the precise targeting of cancerous cells that can be used for therapeutic approaches and live-monitoring of treatment efficacy [43].

#### **4. Radioimmunotherapy (RIT)**

Radioimmunotherapy (RIT) is targeting therapy using radionuclide labeled with specific mAbs directed against tumor antigens [6, 8]. The antibody is primarily a delivery vehicle of radiation to tumors sites. Besides therapy, radionuclide combines with mAbs has been used for imaging. The imaging provides specific non-invasive information regarding the expression, location, and modulation of targets. The therapeutic effect of RIT is achieved by tissue absorption of the energies from continuous radiation emitted from the radionuclides tagged to mAbs. More specific bound between antibody and tumor antigen increase the dose delivered to tumor cells and, at the same time, reduce the dose to normal cells [6]. RIT has been evaluated in clinical trials across the full spectrum of malignancies [8].

The type of radioactive combines with mAb depends on emission characteristics, the radiolabeling chemistry, and the malignancy of cells targeted [8]. Beta and alpha emitter particles are labeled with mAbs. However, alpha emitters have limitations in practice due to mostly very short half-life (**Table 1**) [41]. For optimal therapy, the residence time of RIT ranges from a few days to weeks, which reach optimal tumor-to-background ratios 2–4 days post-injection. Radionuclides labeled mAbs bind several antigens and receptors expressed on the surface of tumor cells. They include CD20, prostate-specific membrane antigen (PSMA), human epidermal growth factor receptor 2+ (HER2+), mucin 1 (MUC1), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), and et cetera [8].

Radioimmunoconjugates targeting CD20 have been approved to treat non-Hodkin's lymphoma (90Y-ibritumomab tiuxetan and 131I-tositumomab) [6, 8]. Both radiolabeled mAbs are more efficacious at inducing remissions than the respective unlabeled molecules and are also more effective than earlier courses of chemotherapy in these patients [8]. Other potentials of RIT include lung, pancreatic, stomach, ovarian, breast, colorectal cancers, leukemia, high-grade brain glioma [6]. On the other hand, the application of RIT for solid tumors has been less successful than in patients with malignant lymphoma. Several problems have to be addressed to its efficacy:


3.Furthermore, 223Ra-chloride showed that these limitations could be successfully circumvented in patients with castration-resistant prostate cancer and bone metastases. RIT therapy may become an effective treatment modality for disseminated solid tumors in the future [8].
