Comparison of the PSMA target efficiency and in vivo biodistribution among [68Ga]ludotadipep, [18F]DCFPyL, and [68Ga]PSMA-11 in a tumor xenograft model

Abstract We have compared the similarity of the in vivo distribution of the prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging agents [ 18 F]DCFPyL, [ 68 Ga]ludotadipep, and [ 68 Ga]PSMA-11. This study is designed for a further selection of a PSMA-targeted PET imaging agent for the therapeutic evaluation of [ 177 Lu]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, [ 68 Ga]PSMA-11 showed the highest uptake in the kidney among all three compounds. [ 18 F]DCFPyL and [ 68 Ga]PSMA-11 showed similar patterns of in vivo biodistribution and high tumor targeting efficiency, similar to those of [ 68 Ga]ludotadipep. All three agents showed high uptake in tumor tissue on autoradiography, and PSMA expression was confirmed by immunohistochemistry. Thus, [ 18 F]DCFPyL or [ 68 Ga]PSMA-11 can be used as a PET imaging agent to monitor [ 177 Lu]ludotadipep therapy in prostate cancer patients.