[161Tb]Tb-PSMA-617 radioligand therapy in patients with mCRPC: preliminary dosimetry results and intra-individual head-to-head comparison to [177Lu]Lu-PSMA-617

Rationale: Evaluation of alternative radionuclides for use in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is currently focusing on 161 Tb, which may provide advantages by emitting additional Auger and conversion electrons.In this pilot study, we present preliminary dosimetry data for [ 161 Tb]Tb-PSMA-617 RLT in a direct comparison with [ 177 Lu]Lu-PSMA-617.Method: Six patients with metastatic castration-resistant prostate cancer (mCRPC) underwent treatment with [ 177 Lu]Lu-PSMA-617 and subsequently -after inadequate response -with [ 161 Tb]Tb-PSMA-617.Whole-body planar and SPECT imaging-based dosimetry of organs at risk (kidneys and salivary glands) and tumor lesions were calculated using IDAC for 177 Lu and OLINDA/EXM for 161 Tb.The therapeutic index (TI) of mean tumor-absorbed doses over relevant organs at risk was calculated.Results: Mean absorbed doses to organs at risk of PSMA-RLT were slightly higher for [ 161 Tb]Tb-PSMA-617 compared to [ 177 Lu]Lu-PSMA-617 (kidneys: 0.643 ± 0.247 vs. 0.545 ± 0.231 Gy/GBq, factor 1.18; parotid gland: 0.367 ± 0.198 vs. 0.329 ± 0.180 Gy/GBq, factor 1.10), but markedly higher regarding tumor lesions (6.10 ± 6.59 vs 2.59 ± 3.30 Gy/GBq, factor 2.40, p < 0.001).Consequently, the mean TI was higher for [ 161 Tb]Tb-PSMA-617 compared to [ 177 Lu]Lu-PSMA-617 for both, the kidneys (11.54 ± 9.74 vs. 5.28 ± 5.13, p = 0.002) and the parotid gland (16.77 ± 13.10 vs. 12.51 ± 18.09, p = 0.008).Conclusion: In this intra-individual head-to-head pilot study, [ 161 Tb]Tb-PSMA-617 delivered higher tumor-absorbed doses and resulted in superior TI compared to [ 177 Lu]Lu-PSMA-617.This preliminary data support 161 Tb as a promising radionuclide for PSMA-RLT in mCRPC.