We present the first metastatic castration-resistant prostate cancer (mCRPC) patient, heavily pretreated with multiple systemic and radioligand therapies, who received [212Pb]Pb-PSMA radioligand therapy (PRLT) combined with the metabotropic glutamate receptor (mGluR)-inhibitor Riluzole due to disease progression. This novel combination, aimed at targeting glutamine addiction in prostate cancer and exploiting radio-sensitization, was well tolerated leading to partial remission of the disease, decrease in PSA values, and stability of symptoms. This represents the first-in-human clinical application of [212Pb]Pb-PSMA PRLT combined with mGluR inhibition in mCRPC, representing a promising therapeutic strategy for advanced, treatment-refractory, progressing patients, supported by molecular imaging and clinical benefit.
Clinical nuclear medicine. 2025 Nov 26 [Epub]
Elisabetta Perrone, Lukas Greifenstein, Kriti Ghai, Ralph Markus Wirtz, Richard Paul Baum
CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Wiesbaden, Germany., STRATIFYER Molecular Pathology GmbH, Cologne, Germany.