What question did this study set out to answer?

The research aims to assess the biodistribution, tolerability, and therapeutic efficacy of [161Tb]Tb-trastuzumab in HER2-expressing breast tumors.

February 16, 2026

In Vivo Studies of 161 TbTb-Trastuzumab Radiopharmaceutical Therapy in Human Epidermal Growth Factor Receptor 2–Expressing Breast Tumors Show High Tumor Uptake and Tumor Growth Suppression

Key Points

The research aims to assess the biodistribution, tolerability, and therapeutic efficacy of [161Tb]Tb-trastuzumab in HER2-expressing breast tumors.
Functionalized trastuzumab was radiolabeled with 161Tb and administered to mice with BT474 tumors.
In vitro assays evaluated binding affinity and immunoreactivity of the radiolabeled compound.
SPECT/CT imaging assessed biodistribution at multiple time points post-injection.
Tolerability was tested with escalating doses of the radiopharmaceutical.
Efficacy was compared to vehicle, trastuzumab, and trastuzumab deruxtecan groups.
Radiolabeling yielded a radiochemical yield of 97% ± 2% and purity above 99%.
Peak tumor uptake was observed 72 hours after injection, with varying dosages resulting in tumor uptake of 10.8 ± 1.1 to 12.8 ± 2.2 %ID/g.
Doses of 20 MBq demonstrated signs of radiotoxicity, whereas lower doses were well tolerated.
A significant reduction in tumor volume was noted with 10 MBq dosage compared to the vehicle group, with <i>P</i> = 0.0007.

Abstract

Human epidermal growth factor receptor 2 (HER2) has emerged as attractive for targeted radionuclide therapy of HER2-expressing breast cancer. The present study aimed to investigate the image-derived biodistribution, tolerability, and efficacy of 161TbTb-trastuzumab as a potential therapeutic alternative or supplement to trastuzumab and trastuzumab deruxtecan in HER2-expressing tumors. Methods: Trastuzumab was functionalized with DOTA by non-site-specific conjugation and radiolabeled with 161Tb. In vitro assays were performed to evaluate binding affinity and immunoreactivity of 161TbTb-trastuzumab. The influence of mass dose on the biodistribution of 161TbTb-trastuzumab was assessed in mice bearing subcutaneous BT474 tumors by SPECT/CT imaging performed 4, 24, 72, and 168 h after injection of 20 MBq of 161TbTb-trastuzumab labeled at 3 specific activities. Tolerability was evaluated with escalating doses of 5, 10, and 20 MBq of 161TbTb-trastuzumab, and the efficacy of 161TbTb-trastuzumab was compared with that of the vehicle, trastuzumab, and trastuzumab deruxtecan groups. Results: Functionalization and radiolabeling resulted in a radiochemical yield of 97% ± 2% and a radiochemical purity above 99%. The binding affinity of functionalized and native trastuzumab was 0.83 and 0.39 nM, respectively, with an immunoreactive fraction of 89%. SPECT/CT imaging demonstrated peak tumor uptake 72 h after injection, with tumor uptake of 10.8 ± 1.1, 12.8 ± 2.2, and 6.3 ± 0.03 %ID/g of tissue for mice dosed with 0.5, 0.05, and 0.005 MBq/µg, respectively. Radiotoxicity was evident in mice dosed with 20 MBq of 161TbTb-trastuzumab, whereas 5 and 10 MBq of 161TbTb-trastuzumab were well tolerated. Antitumor efficacy was observed in mice dosed with 10 MBq of 161TbTb-trastuzumab, which presented tumor volumes statistically significantly smaller than those of the vehicle group 104 d after treatment (P = 0.0007). Conclusion: Functionalization and radiolabeling did not affect binding affinity. Biodistribution of 161TbTb-trastuzumab revealed high tumor uptake of more than 10 %ID/g of tissue, peaking at 72 h. 161TbTb-trastuzumab in doses of up to 10 MBq was tolerated and highly effective at inhibiting tumor growth (P = 0.0007). These results support the potential of 161TbTb-trastuzumab as an attractive treatment option for HER2-expressing cancers.

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