Figure 4.

Cet‐IR700 and pan‐IR700 demonstrate differences in in vivo effects of PIT. (A) Repeated cet‐IR700 mediated PIT leads to less effective A431 tumor volume reduction than pan‐IR700 (cet‐IR700 PIT group vs. pan‐IR700 PIT group after day 12: p < 0.0001) (n = 10 mice in each treatment group; *P < 0.0001, by Kruskal–Wallis test with post‐test). The treatment regimen is shown below the graph. (B) Repeated cet‐IR700 mediated PIT leads to less prolonged survival in A431 tumor bearing mice than with pan‐IR700 (cet‐IR700 PIT group vs. pan‐IR700 PIT group: p < 0.01) (n = 10 mice in each treatment group; **P < 0.0001, by Long‐rank test and Wilcoxon test). (C) Repeated PIT with pan‐IR700 leads to less bioluminescence at 6 h, 3 day, and 4 day after the treatment than cet‐IR700 (n = 7 mice in each treatment group; cet‐IR700 PIT group vs. pan‐IR700 PIT group: ***P < 0.01, ****P < 0.05). The treatment regimen and time points of measurement of bioluminescence are indicated on the left of the graph. (D) Bioluminescence images of MDAMB468‐luc orthotopic tumors in response to repeated PIT with cet‐IR700 or pan‐IR700. Selected mice that had almost the same tumor relative light unit (RLU) before therapy are shown (cet‐IR700; 5479 counts/tumor, pan‐IR700; 5977 counts/tumor). (E) Fluorescence images obtained at each time point before and after repeated PIT. (F) In vivo fluorescence imaging of a A431 xenograft and (G) MDAMB468‐luc orthotopic breast tumor bearing mice treated with repeated PIT showed differences in fluorescence signals in the tumors between treatments with cet‐IR700 and pan‐IR700. Tumors of almost equal size were selected (see magnified view). (H) Tumor‐to‐background ratio (TBR) of the IR700 fluorescence intensity in A431 tumors or MDAMB468‐luc orthotopic breast tumors showed a difference in quantitative uptake and retention (A431; n = 10 mice in each treatment group; *P < 0.05) (MDAMB468‐luc; n = 7 mice in each treatment group).