Work

Preclinical evaluation of 89Zr/177Lu-labelled anti-B7-H3 monoclonal antibody for theranostics in B7-H3-positive liver cancer

Year: 2025

Type: article

Abstract: Liver cancer ranks among the most common cancers with one of the highest mortalities. However, methods for reliable early diagnosis and effective late-stage treatment remain lacking. B7-H3 is an attractive target for the development of immuno-PET and radioimmunotherapy (RIT) for liver cancer due to its association with poor prognosis. A B7-H3-targeting monoclonal antibody (B7-H3mab) labeled with 89 Zr/ 177 Lu may facilitate immunoPET imaging and RIT in liver cancer. Flow cytometry validated the specific binding of B7-H3mab. B7-H3mab was conjugated to p-SCN-Bn-DOTA and p-SCN-Bn-DFO for radiolabeling with 177 Lu and 89 Zr. 177 Lu-DOTA-B7-H3mab and 89 Zr-DFO-B7-H3mab were used for immuno-PET and RIT in subcutaneous liver cancer BALB/C nude mouse models. Flow cytometry analysis demonstrated that Huh7 cells exhibited the highest level of B7-H3 antigen expression on the cell surface and that the antibody's binding capacity remained unchanged after conjugation with DOTA or DFO. The radiochemical purity (RCP) of both 177 Lu-DOTA-B7-H3mab and 89 Zr-DFO-B7-H3mab exceeded 99%. In immuno-PET imaging studies, B7-H3-positive Huh7 tumors exhibited a mean uptake value of 2.47 ± 0.41 (n = 3) at 192 h after injection. The 11.1 MBq group of 177 Lu-DOTA-B7-H3mab significantly reduced tumor growth by 80.2 ± 17.6% (n = 8) at 19 days post-injection. Hematological analysis and hematoxylin and eosin (H&E) staining demonstrated that the side effects were minimal. Labelling B7-H3mab with 89 Zr enabled non-invasive assessment of B7-H3 expression, while 177 Lu labelling effectively suppressed tumour growth in B7-H3-positive liver cancer. Further clinical evaluation of this B7-H3-targeted diagnostic and therapeutic agent may be of significant importance for patients with liver cancer.

Source: European Journal of Pharmaceutical Sciences

DOI: 10.1016/j.ejps.2025.107371