First clinical results with Lu-177 PSMA-TUM1 for the treatment of castrate-resistant metastatic prostate cancer

Objectives EuK-Sub-KFF-DOTAGA (PSMA-TUM1) is a novel ligand targeting the prostate-specific membrane antigen (PSMA). We present the first clinical experience of treating metastatic castrate-resistant prostate cancer (PC) using Lu-177 PSMA-TUM1.

Methods Radioligand therapy (RLT) with Lu-177 PSMA-TUM1 was performed in 6 PC patients with distant metastases and progressive disease, refractory to conventional treatment (including hormone, chemo- and radiation therapy). Ga-68 PSMA-HBED-CC PET/CT was performed in all patients 1-5 days prior to RLT, followed by one therapy cycle (mean administered activity 6.1±1.5 GBq, median 5.8, range 4.2 - 8.6 GBq) of Lu-177 PSMA-TUM1. In addition, early response was evaluated by means of Ga-68 PSMA-HBED-CC PET/CT in 3 patients.

Results Intense PSMA expression by the extensive bone and lymph node metastases (n=4), lung metastases (n=1), residual/ locally recurrent PC (n=2) was confirmed by baseline Ga-68 PSMA-HBED-CC PET/CT. All lesions detected by PET/CT exhibited high Lu-177 PSMA-TUM1 uptake on post-therapy planar and SPECT images. Response evaluation by Ga-68 PSMA-HBED-CC PET/CT revealed excellent treatment response (partial remission) in 2 patients, with decrease in the SUVmax of the target lesion by 51 % and 89 % respectively, and disappearance of many of the previously noted PSMA-positive metastases. There was progression of skeletal metastases in 1 patient. The treatment was well tolerated by all patients without any significant adverse effects or alterations in any of the laboratory parameters.

Conclusions Lu-177 PSMA-TUM1 is a novel and promising radioligand for the treatment of metastatic prostate cancer. Our initial results indicate that RLT is safe and effective, i.e. in combination with patient stratification by Ga-68 PSMA-HBED-CC PET/CT.