Unlocking the Potential of 89Zr/177Lu-Labeled Anti-TROP-2 Antibody for Triple-Negative Breast Cancer Therapy and Imaging

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous cancer that lacks specific treatment targets such as estrogen and progesterone receptors and HER2. Trop-2, a glycoprotein, is overexpressed in a majority of TNBC patients and is linked to disease progression and poor outcomes. This study focused on developing a radiolabeled anti-Trop-2 antibody, NY003, for both immunoPET and SPECT imaging, as well as for radioimmunotherapy (RIT) in a Trop-2 positive TNBC mouse model. The NY003 antibody was engineered based on a camelid antibody and was successfully conjugated with DFO for 89Zr and DTPA for 177Lu labeling. The theranostic efficacy of the radiolabeled NY003 was evaluated through various imaging and RIT studies in mice with Trop-2 positive TNBC tumors.

The study demonstrated that NY003 had a high binding affinity for Trop-2, as confirmed by ELISA. The radiochemical purity of the radiolabeled NY003 was found to be over 95% and was stable for up to 144 hours post-injection in vitro. Both immunoPET and SPECT imaging revealed specific accumulation of the radiolabeled NY003 in MDA-MB-231 tumors, with accumulation increasing over time and being significantly higher than in control groups (P < 0.05). The most potent anti-tumor effects were observed in the group treated with a high dose of 177Lu-DTPA-NY003, with tumor growth significantly inhibited compared to control groups (P < 0.05). Ex vivo biodistribution and histological analysis confirmed the findings from in vivo imaging and RIT studies.

In conclusion, the radiolabeled anti-Trop-2 antibody NY003 serves as a promising platform for radiotheranostics, offering the potential to non-invasively identify patients who may benefit from SG ADC therapy and to suppress the growth of Trop-2 positive TNBC tumors, thus highlighting its theranostic potential.