177Lu-NM600 targeted radionuclide therapy extends survival in syngeneic murine models of triple-negative breast cancer

Triple negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer leading to the worst prognosis. Because current therapeutic approaches lack efficacy, there is a clinically unmet need for effective treatment alternatives. Herein, we demonstrate a promising strategy utilizing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with (177)Lu for targeted radionuclide therapy (TRT) of TNBC. In two murine syngeneic models of TNBC, we confirmed excellent tumor targeting and rapid normal tissue clearance of the PET imaging analog (86)Y-NM600. Based on longitudinal PET/CT data acquired with (86)Y-NM600, we estimated the dosimetry of therapeutic (177)Lu-NM600, which showed larger absorbed doses in the tumor compared to normal tissues. Administration of (177)Lu-NM600 resulted in significant tumor growth inhibition and prolonged overall survival in mice bearing syngeneic 4T07 and 4T1 tumors. Complete response was attained in 60% of 4T07 bearing mice, but animals carrying aggressive 4T1 tumor grafts succumbed to metastatic progression. The injected activities used for treatment (9.25 and 18.5 MBq) were well tolerated, and only mild transient cytopenia was noted. Overall, our results suggest that (177)Lu-NM600 TRT has potential for treatment of TNBC and merits further exploration in a clinical setting.