Biodistribution and dosimetry of Lu-177 PSMA in metastasized castrate resistant prostate cancer patients

641 Objectives The prostate specific membrane antigen (PSMA) is significantly over-expressed in prostate cancer cells as compared to normal prostate. The aim of our study was to determine the kinetics and dosimetry of the recently developed Lu-177 labeled PSMA ligand EuK-Sub-KFF-DOTAGA (PSMA-TUM1) for therapy of metastasized prostate cancer. Methods Six patients with metastasized prostate cancer (69+/-8 years) with high PSMA expression (confirmed previously by Ga-68 PSMA-HBED PET/CT) underwent radioligand therapy with 4.2-8.6 GBq Lu-177 PSMA-TUM1. Based on 5 post-therapy whole-body scans, the kinetics in tumors and normal tissues were determined and dosimetric calculations performed (MIRD scheme and OLINDA/EXM). Blood samples were drawn to determine the plasma clearance and to estimate the absorbed dose to red marrow. Results An intense uptake in the tumor lesions as well as significant renal accumulation was noted in all patients. The whole-body uptake showed an exponential decline with a half-life of 24-91hours. The renal uptake ranged from 3 to 5% IA (% of injected activity) and showed a fast washout with a half-life of 20-57 hours. The accumulation in lymph node and bone metastases followed an exponential decline with half-life of 52 -149 hours. The following organ and tumor doses were calculated: whole body 0.02+/-0.01mGy/MBq; kidneys 0.33+/-0.15mGy/MBq; tumor lesions 0.14-5.5mGy/MBq. There was rapid blood clearance with a half-life of up to 42 hrs. Conclusions Based on the high tumor uptake of Lu-177 PSMA-TUM1, its fast renal washout, the rapid blood clearance and its favorable dosimetry, radioligand therapy using Lu-177 PSMA-TUM1 appears to be a new promising therapy option of metastasized castrate resistant prostate cancer. Further clinical studies based on a larger number of patients are necessary to validate these results.