This study presents the first human 212Pb SPECT/CT images acquired in a patient with metastatic castration-resistant prostate cancer. The patient, a 73-year-old man, received 60 MBq of 212Pb-ADV001, and imaging was performed at 1.5, 5, 20, and 28 hours post-infusion. The images, obtained using a Siemens Intevo Bold with high-energy collimators, showed rapid tumor uptake of 212Pb-ADV001, which was highly concordant with the tumor burden as seen on pretreatment 18F-DCFPyL PET/CT images. Despite low counts due to 212Pb decay (10.6-hour half-life), persistent tumor uptake was observed at 20 hours. The study demonstrates the feasibility and benefits of 212Pb SPECT/CT imaging for post-infusion radiopharmaceutical biodistribution and patient-specific dosimetry, which is crucial for the clinical development of 212Pb-targeted α-therapy.This study presents the first human 212Pb SPECT/CT images acquired in a patient with metastatic castration-resistant prostate cancer. The patient, a 73-year-old man, received 60 MBq of 212Pb-ADV001, and imaging was performed at 1.5, 5, 20, and 28 hours post-infusion. The images, obtained using a Siemens Intevo Bold with high-energy collimators, showed rapid tumor uptake of 212Pb-ADV001, which was highly concordant with the tumor burden as seen on pretreatment 18F-DCFPyL PET/CT images. Despite low counts due to 212Pb decay (10.6-hour half-life), persistent tumor uptake was observed at 20 hours. The study demonstrates the feasibility and benefits of 212Pb SPECT/CT imaging for post-infusion radiopharmaceutical biodistribution and patient-specific dosimetry, which is crucial for the clinical development of 212Pb-targeted α-therapy.