FIGURE 5.

[¹⁷⁷Lu]Lu-DOTA-trastuzumab uptake and cytotoxic effects when combined with Gd-NPs. (A) [¹⁷⁷Lu]Lu-DOTA-trastuzumab uptake in SK-OV-3-luc cells incubated with radiolabeled antibody, 1 MBq/mL, for 18 h. (B and C) Clonogenic survival of SK-OV-3-luc (B) and A-431 (C) cells incubated with [¹⁷⁷Lu]Lu-DOTA-trastuzumab (0–4 MBq/mL) with or without Gd-NPs, 10 mg/mL, for 18 h. Results are mean ± SD of 3 independent experiments performed in triplicate. Role of oxidative stress in Gd-NP radiosensitizing effect was demonstrated using N-acetyl-l-cysteine, catalase, and dimethyl sulfoxide (Fig. 6A). Indeed, when SK-OV-3-luc cells were coincubated with Gd-NPs and each of these antioxidants, clonogenic survival increased. These results were confirmed using deferiprone, an iron chelator that prevents reactive oxygen species formation (Fig. 6B). *P < 0.05. **P < 0.01. ***P < 0.001. ****P < 0.0001. inc = incubation time (18 h); ns = not significant (Mann–Whitney t test).