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 89Zr/177Lu 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 177Lu and 89Zr. 177Lu-DOTA-B7-H3mab and 89Zr-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 177Lu-DOTA-B7-H3mab and 89Zr-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 177Lu-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 89Zr enabled non-invasive assessment of B7-H3 expression, while 177Lu 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.