Figure 5.

ICAM-1-targeted imaging identifies VS-6063 as a novel adjuvant to enhance the systemic antitumor effect of RT. (A) Schedule of WT BALB/c mice bearing 4T1 tumors treated with X-ray RT in combination with different small-molecule drugs, listed in Table S1. (B) Representative NIRF images of Dye-αICAM-1/Fab at 6 h postinjection in the 4T1 tumor-bearing mice on days 10, 13, and 17 after combined X-RT with different drugs as described in (A) (n = 3 per group). (C) The average Dye-αICAM-1/Fab uptake ratio of distant tumor-to-muscle at 6 h postinjection relative to the baseline values (day 10) in 4T1 tumor-bearing mice on days 13 and 17 after indicated treatments as described in (A). (D, E) Small-animal PET images (D) and quantified tumor (distant tumor) uptake (E) of ⁸⁹Zr-DFO-αICAM-1/Fab at 24 h postinjection in 4T1 tumor-bearing mice after the indicated treatments (n = 5 per group). Distant tumors are indicated by red circles. (F) Western blotting images and quantification analysis of ICAM-1 levels in 4T1 tumor tissues on day 16 after X-RT plus VS-6063 treatment (n = 4 per group). (G) Schedule of combined RT with VS-6063 treatment in BALB/c mice bearing bilateral 4T1 tumors. (H-J) Average tumor growth curves of primary tumors (H) and distant tumors (I), and body weight (J) of 4T1 tumor-bearing mice after indicated treatments as illustrated in (G) (n = 6-7 per group). Data are represented as mean ± SD. P values were determined using unpaired Student's t-test (E, F, H, I). NS, not significant (P > 0.05).