Claudin 6 (CLDN6) is highly expressed in ovarian cancer (OV) and uterine corpus endometrial cancer (UCEC) but silenced in normal tissues, holding promise as an attractive target for radioimmunotherapy (RIT). This study aimed to develop zirconium-89 (⁸⁹Zr)/lutetium-177 (¹⁷⁷Lu)-labeled CLDN6 antibody (IMAB027) for immuno-positron emission tomography (immuno-PET) and RIT for OV and UCEC subcutaneous tumor models. IMAB027 was conjugated with p-SCN-Bn-DFO and DOTA-maleimide, followed by radiolabeling with 89Zr/177Lu. In immuno-PET, [⁸⁹Zr]Zr-DFO-IMAB027 specifically accumulated in tumor regions, reaching maximum uptake at 96 h post-injection and maintaining elevated levels, consistent with biodistribution results. [¹⁷⁷Lu]Lu-DOTA- IMAB027 exhibited high radioactive binding efficiency through cell binding, blocking, and internalization assays. And the 11.1 MBq [¹⁷⁷Lu]Lu-DOTA-IMAB027 group significantly inhibited tumor growth, prolonged survival, and showed lower toxicity than non-radioactive drug treatment groups. ⁸⁹Zr/¹⁷⁷Lu-labeled IMAB027 holds promise as a potentially viable therapeutic approach for clinical management of gynecological cancers.