figure a

Brain metastases are not common in prostate cancer; they typically occur in patients with end-stage disease who are castrate-resistant. Patients with brain metastases have very limited survival [1]. Traditionally, the mainstays of therapy have been surgical resection, chemotherapy and external beam radiotherapy. Recently, combination of 177Lu-Prostate-specific membrane antigen (PSMA)-617 and external radiotherapy for the treatment of cerebral metastases in patients with castration-resistant metastatic prostate cancer (mCRPC) showed significant regression in the sizes and PSMA-ligand avidity of the lesions over time [2]. Recent studies have demonstrated that targeted α-radiation therapy with 225Ac-PSMA-ligand can significantly benefit patients with mCRPC in the appropriate setting [3, 4]. Targeted α-radiation therapy may be more effective for the treatment of mCRPC, and has been shown, in a limited number of patients, to be effective in the setting of resistant to 177Lu-PSMA-617 therapy [5].

We present a remarkable response of prostate cancer cerebral metastases following treatment with 225Ac-PSMA-617 in a patient with mCRPC whose disease progressed under androgen deprivation with Goserelin and chemotherapy with docetaxel. Initial assessment with 68Ga-PSMA-ligand PET/CT showed tracer-avid cerebral metastases and widespread skeletal metastases (Fig. 1a). The patient was treated with one cycle of 225Ac-PSMA-617 with an activity of 8 MBq. Restaging with 68Ga-PSMA-ligand PET/CT after one cycle showed a remarkable functional response (resolution of cerebral and extensive skeletal metastases) and biochemical response (decrease in serum PSA level from 788.63 μg/L to 6.52 μg/L) (Fig. 1b). Four months later, the serum PSA dropped to 0.32 μg/L after a second cycle of therapy with 225Ac-PSMA-617. This case highlights the potential of 225Ac-PSMA-617 for treatment of brain metastases of mCRPC in patients with limited treatment option.