RT Journal Article SR Electronic T1 177Lu-NM600 targeted radionuclide therapy extends survival in syngeneic murine models of triple-negative breast cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.119.236265 DO 10.2967/jnumed.119.236265 A1 Hernandez, Reinier A1 Grudzinski, Joseph J A1 Aluicio-Sarduy, Eduardo A1 Massey, Christopher F A1 Pinchuk, Anatoly N A1 Bitton, Ariana N A1 Patel, Ravi A1 Zhang, Ray A1 Kumar, Aakarsha V A1 Iyer, Gopal A1 Engle, Jonathan W A1 Weichert, Jamey P YR 2019 UL http://jnm.snmjournals.org/content/early/2019/12/20/jnumed.119.236265.abstract AB 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 177Lu 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 86Y-NM600. Based on longitudinal PET/CT data acquired with 86Y-NM600, we estimated the dosimetry of therapeutic 177Lu-NM600, which showed larger absorbed doses in the tumor compared to normal tissues. Administration of 177Lu-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 177Lu-NM600 TRT has potential for treatment of TNBC and merits further exploration in a clinical setting.