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[161Tb]Tb-DOTATATE as a potential treatment option for neuroblastoma
Saloni Chopra1, Tianqi Xu1, Hanna Berglund1
1Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85, Uppsala, Sweden.
Background:
Neuroblastoma is an aggressive paediatric malignancy with poor outcomes in high-risk patients despite multimodal therapy. [177Lu]Lu-DOTATATE, targeting somatostatin receptor 2 (SSTR2), is under clinical investigation for neuroblastoma. Terbium-161 (161Tb) shares chemical characteristics and a similar half-life with lutetium-177 (177Lu) but offers advantages through its higher emission of Auger and conversion electrons, which may enhance therapeutic efficacy especially for micrometastases and recurrent disease. This study investigates [161Tb]Tb-DOTATATE as a potential complement for treatment of SSTR2-expressing neuroblastoma.
Results:
DOTATATE was successfully radiolabelled with 161Tb, achieving high radiochemical yield and stability. [161Tb]Tb-DOTATATE demonstrated clear SSTR2-specific binding in vitro, as well as biodistribution and tumour uptake comparable to [177Lu]Lu-DOTATATE in vivo. Treatment with [161Tb]Tb-DOTATATE reduced tumour growth in an activity-dependent manner, and demonstrated stronger early tumour control compared to [177Lu]Lu-DOTATATE at comparable administered activities (**p < 0.01 at day 9). Tumour doubling times were longest in the 6 MBq [161Tb]Tb-DOTATATE group (29 vs. 18 days in controls), while the 3 MBq [161Tb]Tb-DOTATATE group showed similar doubling times to 4 MBq [177Lu]Lu-DOTATATE (21 vs. 22 days). This was also reflected in survival, where 6 MBq [161Tb]Tb-DOTATATE achieved the greatest effect (50% increase in median survival), followed by 4 MBq [161Tb]Tb-DOTATATE (36%), while 3 MBq [161Tb]Tb-DOTATATE and 4 MBq [177Lu]Lu-DOTATATE showed more modest improvements (23%). All treatment regimens were well tolerated, and no signs of treatment-related toxicity were observed.
Conclusion:
[161Tb]Tb-DOTATATE demonstrates favourable targeting properties and activity-dependent therapeutic efficacy in preclinical neuroblastoma models without detectable toxicity. These findings encourage us to explore its potential as a complement to [177Lu]Lu-DOTATATE, particularly for targeting minimal residual disease and micrometastases, and warrant further preclinical and clinical evaluation.
