Fig. 4
In vivo photoimmunochemotherapy for human gastric cancer xenografts. a Experimental protocol of photoimmunochemotherapy in vivo. (a) No treatment, (b) 30 μg/g/day of 5-fluorouracil (5-FU) i.p. without near-infrared (NIR) light irradiation, (c) 300 μg of trastuzumab-IR700 conjugate (Tra-IR700) i.v. without NIR light irradiation, (d) NIR light irradiation (100 J/cm2) without 5-FU or Tra-IR700 injection, (e) 30 μg/g/day of 5-FU i.p. and 300 μg of Tra-IR700 i.v. without NIR light irradiation, (f) 30 μg/g/day of 5-FU i.p. followed by NIR light irradiation (100 J/cm2), (g) 300 μg of Tra-IR700 i.v. followed by NIR light irradiation (100 J/cm2), and (h) 30 μg/g/day of 5-FU i.p. and 300 μg of Tra-IR700 i.v. followed by NIR light irradiation (100 J/cm2). Tra-IR700 injection was performed at the time of mouse randomization (Day 0), and NIR light irradiation was performed 24 h after Tra-IR700 injection (Day 1). Injection of 5-FU was performed on 3 consecutive days (Day 1 [just after NIR light irradiation], Day 2, and Day 3; total amount, 90 μg/g). Open downwards arrow: 300 μg of Tra-IR700 i.v.; filled upwards arrow: 30 μg/g of 5-FU i.p. b Photoimmunochemotherapy resulted in marked antitumor effects compared to photoimmunotherapy (PIT) alone. A significant therapeutic effect was observed in mice treated with PIT in combination with 5-FU compared to in mice treated with PIT alone on Days 24 and 26 after the initial treatment. Data are presented as means ± SEM (at least n = 10 mice in each group, * P < 0.05 vs. treated with PIT alone, Mann–Whitney U test). c Histological observations of the negative control and treated NCI-N87 tumors (n = 3 mice, hematoxylin and eosin staining). Bleeding and massive granulation with inflammatory changes were observed, and only scant viable cells were present in the tumor nodules treated with PIT in combination with 5-FU. Scale bar, 100 μm