Terbium-161, a Promising New Theranostic Radionuclide

Introduction: Peptide receptor radionuclide therapy (PRRT) has recently risen to popularity as a method of cancer treatment. Prostate-specific membrane antigen (PSMA) and somatostatin receptors (SSTRs) have been shown to be effective targets for radionuclide therapy. Terbium-161 (¹⁶¹Tb) is similar to Lutetium-177 (¹⁷⁷Lu) in its half-life and decay processes, which include β ̄-particles and γ-ray emission. In comparison, ¹⁶¹Tb is a more effective therapy agent than ¹⁷⁷Lu because of its substantial emission of conversion and Auger electrons.

Multiple ongoing clinical trials are investigating the safety and efficacy of medicines involving ¹⁶¹Tb. A Phase I clinical trial aims to establish the safety profile, dosimetry, and maximum tolerated dose (MTD) of ¹⁶¹Tb-PSMA-I&T in patients with metastatic castration-resistant prostate cancer (mCRPC). Phase II examines the effectiveness of the radiopharmaceutical at the MTD and gathers evidence of therapeutic advantages in targeted patient groups.

Methods: The synthesizing process and quality control of ¹⁶¹Tb-DOTATOC are completely automated. Automation streamlines the manufacturing process, lowers radiation exposure, and facilitates clinical translation. The production process takes 45 minutes and has the capability to generate a dose comparable to ¹⁷⁷Lu-DOTATOC with 98% radiochemical purity.

Results: When evaluating a circulating tumor cell (CTC) derived from a prostate cancer patient averaging the size of 7.97 µm, ¹⁶¹Tb delivers approximately 3.5 times higher radiation dosage to the cell, while emitting radiation that is equivalent to that of larger cells.

When ¹⁶¹Tb is compounded with DOTATOC, it shows the same biodistribution as ¹⁷⁷Lu-DOTATOC. The selectivity for subtype 2 (SSTR2) is retained and is comparable to ¹⁷⁷Lu.

¹⁶¹Tb has the potential for PSMA targeted radionuclide therapy in prostate cancer through specific absorption of the radioligand at the tumor, resembling the uptake pattern observed with ¹⁷⁷Lu-PSMA-617. ¹⁶¹Tb exhibited 1.3 times higher absorption compared to ¹⁷⁷Lu. The efficacy of ¹⁶¹Tb induced cancer cell death was superior. Increasing the dosage of ¹⁶¹Tb by two-fold led to a decrease in the median survival time, indicating a direct relationship between the dosage and survival duration. Tumor-targeting agents labeled with ¹⁶¹Tb effectively delayed tumor growth.

Conclusions: Comparative studies demonstrate ¹⁶¹Tb's greater radiation dose delivery and effectiveness, particularly in smaller tumor spheres and circulating tumor cells. In comparison to ¹⁷⁷Lu SST and PSMA analogs, ¹⁶¹Tb demonstrates matching biodistribution with comparable selectivity. The preclinical results for ¹⁶¹Tb demonstrate significant potential for improving treatment options. Leveraging preclinical data and innovative trial designs, ¹⁶¹Tb is a promising new theranostic radionuclide.