Evaluation of Fluorescence Intensity and Antitumor Effect Using Real-Time Imaging in Photoimmunotherapy

Abstract

Photoimmunotherapy (PIT) is a promising tumor-selective treatment method that uses light-absorbing dye-conjugated antibodies and light irradiation. It has been reported that IR700 fluorescence changes with light irradiation. The purpose of this study was to investigate the fluorescence intensity and antitumor effect of PIT using real-time fluorescence observation of tumors and predict the required irradiation dose. The near-infrared camera system LIGHTVISION was used to image IR700 during PIT treatment. IR700 showed a sharp decrease in fluorescence intensity in the early stage of treatment and almost reached a plateau at an irradiation dose of 40 J/cm. Cetuximab-PIT for A431 xenografts was performed at multiple doses from 0–100 J/cm. A significant antitumor effect was observed at 40 J/cm compared to no irradiation, and there was no significant difference between 40 J/cm and 100 J/cm. These results suggest that the rate of decay of the tumor fluorescence intensity correlates with the antitumor effect by real-time fluorescence imaging during PIT. In addition, when the fluorescence intensity of the tumor plateaued in real-time fluorescence imaging, it was assumed that the laser dose was necessary for treatment.

Near-Infrared Fluorescence Imaging Sensor with Laser Diffuser for Visualizing Photoimmunotherapy Effects under Endoscopy

“…Takashima et al conducted a study using nine mice in a fluorescence imaging experiment and found that the fluorescence decayed rapidly after irradiation and reached equilibrium between 150 and 330 s, maximizing the anti-tumor effect [ 14 ]. As the present results exhibited similar behavior, the obtained fluorescence images were considered reliable.…”

“…Previous research by Sato et al reported that the fluorescence of Cet-IR700 can be observed by NIR light exposure [ 12 , 13 ]. Takashima et al used a fluorescence imaging system (LIGHTVISION, SHIMADZU, Japan) to visualize the real-time drug accumulation of light-sensitive substances in tumors, and they demonstrated a correlation between the decay rate of the fluorescence intensity and the anti-tumor effect [ 14 ]. However, current endoscopes are unable to employ the configuration that is required for fluorescence observation when treatment is performed, especially in the digestive tract.…”

Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy

“…Therefore, 50 J/cm 2 , the light dose at which the intratumor fluorescence disappeared completely, was considered to be the saturation dose in this experiment, and theoretically no improved therapeutic effect is expected by increasing the light dose above this saturation dose. The relationship between fluorescence imaging and therapeutic efficacy in an immunocompromised mouse model using the A431 tumor and Cetuximab has recently been reported [ 23 ]. In the article, the authors concluded that approximately 40 J/cm 2 was the light dose with saturating NIR-PIT therapeutic effects.…”

Near-Infrared Fluorescence Imaging Sensor with Laser Diffuser for Visualizing Photoimmunotherapy Effects under Endoscopy

“…Previous research by Sato et al reported that the fluorescence of Cet-IR700 can be observed by NIR light exposure [12,13]. Takashima et al used a fluorescence imaging system (LIGHTVI-SION, SHIMADZU, Japan) to visualize the real-time drug accumulation of light-sensitive substances in tumors, and they demonstrated a correlation between the decay rate of the fluorescence intensity and the anti-tumor effect [14]. However, current endoscopes are unable to employ the configuration that is required for fluorescence observation when treatment is performed, especially in the digestive tract.…”