In vitro and in vivo response of PSMA-617 radiolabeled with CA and NCA lutetium-177

The PSMA-targeted radionuclide therapy has been explored since 2015 with radioisotope lutetium-177, whose β− emission range is adequate for micrometastases treatment. This radioisotope is obtained by two different production routes that directly affect the specific activity of lutetium-177 (non-carrier added and carrier added) and, consequently, the specific activity of radiopharmaceuticals, like 177Lu-PSMA-617. The influence of the specific activity of lutetium-177 on the properties of the radiopharmaceutical PSMA-617 was evaluated through pre-clinical studies. The in vitro study pointed to a lower constant of dissociation with non-carrier added lutetium-177 due to the difference in the specific activity. However, competition and internalization assays resulted in similar results for both lutetium-177. Based on these pre-clinical experiments, the total in vitro tumor cell binding and tumor uptake in vivo were similar, with no influence of the specific activity of the 177Lu-PSMA-617. Regardless the specific activity did not directly affect tumor uptake, the tumor/non-target organs ratios were higher for the radiopharmaceutical labeled with carrier added lutetium-177, which had the lowest specific activity. •In vitro and in vivo comparison of PSMA-617 radiolabeled with NCA and CA lutetium-177.•Competition and internalization assays demonstrated no difference between PSMA-617 radiolabeled with NCA or CA lutetium-177.•PSMA-617 radiolabeled at a lower specific activity (CA lutetium-177) showed the best ratio of tumor to non-target organs.