Initial Multicenter Experience with [¹⁶¹Tb]Tb-PSMA in [¹⁷⁷Lu]Lu-PSMA-Refractory Metastatic Castration-Resistant...

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Therapy

Background:

• ¹⁶¹Tb is a theranostic radionuclide with high linear energy transfer, offering potential for enhanced cytotoxicity in micrometastatic disease.
• Metastatic castration-resistant prostate cancer (mCRPC) poses treatment challenges, especially after progression on standard therapies like Lu-177 PSMA.

Purpose of the Study:

• To evaluate the first multicenter clinical experience of ¹⁶¹Tb-PSMA in patients with mCRPC refractory to ¹⁷⁷Lu-PSMA therapy.
• To assess the safety, efficacy, and dosimetry of ¹⁶¹Tb-PSMA in this patient population.

Main Methods:

• Prospective, multicenter study involving 7 mCRPC patients previously treated with ¹⁷⁷Lu-PSMA.
• Patients received 2 cycles of ¹⁶¹Tb-PSMA, with response assessed by ¹⁸F-FDG PET/CT, PSA kinetics, and dosimetry via SPECT/CT.

Main Results:

• 4 out of 7 patients (57%) showed objective imaging response.
• 4 out of 7 patients (57%) achieved at least a 50% decline in PSA levels.
• Treatment was well-tolerated with mild adverse events (grades 1-2) and favorable organ dosimetry.

Conclusions:

• ¹⁶¹Tb-PSMA demonstrated promising molecular and biochemical activity in mCRPC patients progressing after ¹⁷⁷Lu-PSMA therapy.
• The favorable safety profile supports further investigation of ¹⁶¹Tb-based radiopharmaceuticals as next-generation therapies for mCRPC.