Abstract: Due to the specific characteristics of high linear energy transfer(80-100 keV/μm), short penetration distance(40-100 μm), strong cytotoxic and few reverse effects, α radionuclides has a promising prospect for the therapy of micro-tumors, primary and micro-metastatic cancers. As the parent nuclide of the alpha-emitting radioisotope ²¹²Bi, ²¹²Pb has been attracted much attention in the application of targeted alpha therapy. Compared with ²²⁵Ac, ²¹²Pb only involves one alpha decay. This ensures that therapeutic energy is delivered precisely and reduces the damage to the surrounding healthy tissues. In addition, Pb has a strong coordination ability and is more likely to combine with small molecule ligands to form stable targeted drugs. Thus, in recent years, researchers have prepared ²¹²Pb radiopharmaceuticals by combining ²¹²Pb with monoclonal antibodies, peptides, nanoparticles, etc. This paper summarizes the properties and preparation techniques of ²¹²Pb nuclides, and the properties of chelators between ²¹²Pb and targeted ligands. Three different ways of preparation technologies for separating and extracting of ²¹²Pb are described: through ²³²Th or ²³²U, reactor irradiation of ²²⁶Ra. In contrast, there are some advantages to produce ²¹²Pb by the third method. The extraction efficiency of ²²⁸Th can be increased and the loss of ²²⁶Ra is extremely low during the preparation process. Then, this article describes the ²¹²Pb-complexes with DOTA, NOTA, TCMC, p-SCN-Bn-TCMC. The research progress and current clinical application of ²¹²Pb radiopharmaceuticals, such as ²¹²Pb-DOTAMTATE, ²¹²Pb-ADVC001, ²¹²Pb-DOTAM-GRPR1, ²¹²Pb-VMT-α-NET, are also discussed. In addition, ²⁰³Pb, as an easily accessible diagnostic nuclide, can be used in combination to provide accurate data for the ²¹²Pb treatment, which can further increase the application of ²¹²Pb radiopharmaceuticals in the clinical. The rapid development of ²¹²Pb radiopharmaceuticals has highlighted their potential as a form of radiotherapy and their remarkable effects in treating a variety of diseases. It is expected to be a support for providing references for the researches and applications in the treatment of malignant tumors in the future. Meanwhile, it should be noted that a large amount of research is still needed before it can be used for human treatment in the hospital, including production and transportation of ²¹²Pb nuclides, the recoil phenomenon of decayed nuclides, the visual monitoring of drug distribution during treatment, the estimation of radiation doses, the assessment of toxicity, and the setting of standard doses, etc. Although large-scale clinical research is still needed, we should believe that ²¹²Pb radiopharmaceuticals can play a significant role in the future with the continuous development of nuclear and medical technologies.