Figure 4A. (Top) Balb/cJ mice were engrafted with EMT6 cells by subcutaneous injection of 1 million cells. After 5 days, animals were treated by IV injection of PBS, DOTA-NP137 or NP137-177Lu. n = 9 animals/group for PBS and DOTA-NP137; n = 12 animals/group for NP137-177Lu; p < 0.001 between PBS and NP137-177Lu and between DOTA-NP137 and NP137-177Lu (Two-way ANOVA) between PBS and NP137-177Lu and between DOTA-NP137 and NP137-177Lu. Error bars indicate s.e.m.. (Bottom) NP137-177Lu survival of mice engrafted with EMT6 cells. Kaplan-Meier survival curves of mice treated or not with DOTA-NP137. Mantel Cox test; n = 9 animals/group for PBS and DOTA-NP137; n = 12 animals/group considered as dead at a tumor volume of 2,000mm3 for NP137-177Lu; p < 0.001 between PBS and NP137-177Lu and between DOTA-NP137 and NP137-177Lu. B. (Top) Balb/c mice were engrafted with 4T1 cells by subcutaneous injection of 1 million cells. After 8 days, animals received IV injections of PBS, DOTA-NP137 or NP137-177Lu; n = 10 animals/group for PBS and DOTA-NP137; n = 9 animals/group for NP137-177Lu; p < 0.001 between PBS and NP137-177Lu and between DOTA-NP137 and NP137-177Lu (Two-way ANOVA). Error bars indicate s.e.m.. (Bottom) NP137-177Lu survival of mice engrafted with 4T1 cells. Kaplan-Meier survival curves of mice treated or not with DOTA-NP137. Mantel Cox test; n = 10 animals/group for PBS and DOTA-NP137; n = 9 animals/group considered as dead at a tumor volume of 2,000 mm3 for NP137-177Lu; p = 0.002 between PBS and NP137-177Lu and between DOTA-NP137 and NP137-177Lu. C. (Top) NMRI nude mice were engrafted with H358 cells by subcutaneous injection of 5 million cells and considered as dead when tumor volume reached 2,000mm3. After 15 days, animals were treated by IV injection of PBS, DOTA-NP137 or NP137-177Lu; n = 8 animals/group for PBS and DOTA-NP137; n = 9 animals/group for NP137-177Lu; p < 0.001 between PBS and NP137-177Lu and between DOTA-NP137 and NP137-177Lu (2-way ANOVA) between PBS and NP137-177Lu and between DOTA-NP137 and NP137-177Lu. Error bars indicate s.e.m. (Bottom) NP137-177Lu survival of mice engrafted with H358 cells.. Kaplan-Meier survival curves of mice treated or not with DOTA-NP137. Mantel Cox test; n = 8 animals/group for PBS and DOTA-NP137; n = 9 animals/group for NP137-177Lu; p = 0.025 between PBS and NP137-177Lu and between DOTA-NP137 and NP137-177Lu.D. (Left) Quantification of Ki67 expression in EMT6 tumors harvested in Balb/cJ mice 7 days post injection of PBS, DOTA-NP137 or NP137-177Lu. (Right) Representative bright field micrographs of Ki67 immunohistochemistry in formalin-fixed paraffin-embedded EMT6 tumors harvested in Balb/cJ mice 7 days post injection of PBS, DOTA-NP137 or NP137-177Lu; n = 4 mice per groups; One-way ANOVA. Error bars indicate s.e.m. Scale bar: 50μm. E. (Left) Quantification of cleaved caspase-3 expression in EMT6 tumors harvested in Balb/cJ mice 7 days post injection of PBS, DOTA-NP137 or NP137-177Lu. (Right) Representative bright field micrographs of cleaved caspase-3 immunohistochemistry in formalin-fixed paraffin-embedded EMT6 tumor harvested in Balb/cJ mice 7 days post injection of PBS, DOTA-NP137 or NP137-177Lu; n = 4 mice per groups; One-way ANOVA. Error bars indicate s.e.m. Scale bar:.50μm.