In vivo efficacy studies evaluating single and fractionated dosing regimens of [211At]MM4 in an IMR-05 xenograft mouse model. Tumor growth and Kaplan-Meier curves for IMR-05 tumor bearing mice treated with A) single dose of 555 or 1,110 kBq of [211At]MM4 (control vs. 555 kBq and 1110 kBq mixed linear model p-value < 0.0001; control vs. 555 kBq and 1110 kBq survival mantel cox test p-value < 0.0001, 555 KBq vs. 1110 kBq not significant), and B) single high dose of 1480 kBq vs. a fractionated dose of 370 kBq twice weekly for a cumulative dose of 1480 kBq (control vs. fractionated mixed linear model p-value < 0.0001, fractionated vs. high dose not significant; survival mantel cox test high dose vs. control p-value < 0.0001, fractionated vs. control p-value = 0.03). C) Toluadine blue stains on control vs. fractionated therapy treated tumor sections. D) Control vs. treated tumor from the in vivo efficacy study evaluating fractionated vs. single high dose therapy. Immunofluorescence on tumor sections were performed for PARP-1 and Ki-67. E) Tumor sections fluorescently stained for PARP-1 taken from IMR-05 tumor bearing mice treated with 370 kBq of [211At]MM4 at 24, 48, and 72 h after treatment (t-test, p-value < 0.001 (24 h), 0.05 (72 h).
* denote statistical significance described in the figure legend.