Evaluation of PSMA target diagnostic PET tracers for therapeutic monitoring of [177Lu]ludotadipep of prostate cancer: Screening of PSMA target efficiency and biodistribution using [18F]DCFPyL and [68Ga]PSMA-11

We have compared the similarity of the in vivo distribution of the prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging agents [18F]DCFPyL, [68Ga]galdotadipep, and [68Ga]PSMA-11. This study is designed for a further selection of a PSMA-targeted PET imaging agent for the therapeutic evaluation of [177Lu]ludotadipep, our previously developed prostate-specific membrane antigen (PSMA)-targeted prostate cancer therapeutic radiopharmaceutical. In vitro cell uptake was performed to evaluate the affinity to PSMA using PSMA + PC3-PIP, and PSMA− PC3-flu was used for the study. MicroPET/CT 60 min dynamic imaging and biodistribution were performed at 1, 2, and 4 h after injection. Autoradiography and immunohistochemistry were performed to evaluate the PSMA + tumor target efficiency. In the microPET/CT image, [68Ga]PSMA-11 showed the highest uptake in the kidney among all three compounds. [18F]DCFPyL and [68Ga]PSMA-11 showed similar patterns of in vivo biodistribution and high tumor targeting efficiency, similar to those of[68Ga]galdotadipep. All three agents showed high uptake in tumor tissue on autoradiography, and PSMA expression was confirmed by immunohistochemistry. Thus, [18F]DCFPyL or [68Ga]PSMA-11 can be used as a PET imaging agent to monitor [177Lu]ludotadipep therapy in prostate cancer patients.