Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a newly-established cancer treatment which employs the combination of an antibody-photoabsorber conjugate (APC) and NIR light. When NIR light is absorbed by APC-bound tissues, a certain amount of heat is generated locally. For the most part this results in a subclinical rise in skin temperature, however, excessive light exposure may cause non-specific thermal damage. In this study, we investigated the potential for thermal damage caused by NIR-PIT by measuring surface temperature. Two sources of light, laser and light emitting diode (LED), were compared in a mouse tumor model. First, we found that the skin was heated rapidly by NIR light regardless of whether laser or LED light sources were used. Air cooling at the surface reduced the rise in temperature. There were no associations between the rise of skin temperature and tumor volume of the treated tumor, or APC concentration. Second, we investigated the extent of thermal damage to the skin at various light doses. We detected burn injuries 1 day after NIR-PIT, when the NIR light was at a power density higher than 600 mW/cm2. Successful treatments at lower power density could be achieved if the total light energy absorbed by the tumor was the same, i.e. by extending the duration of light exposure. In conclusion, this study demonstrates that thermal injury after NIR-PIT can be avoided by either employing a cooling system or by lowering the power density of the light source and prolonging the exposure time such that the total energy is constant. Thus, thermal damage is preventable side effect of NIR-PIT.

Highlights

  • Near infrared photoimmunotherapy (NIR-PIT) is a newly-established cancer therapy utilizing an antibodyphotoabsorber conjugate (APC), which binds to antigens expressed on the cellular membrane of cancer cells

  • In order to investigate the relationship between temperature changes at tissues and NIR light dose (whether from laser or light emitting diode (LED)), the temperature of mouse skin was measured during Near-infrared photoimmunotherapy (NIR-PIT) via a thermal imaging system (Figure 1)

  • The change in temperature was compared with or without air cooling using a desktop fan. Both NIR exposure with the laser and the LED caused the mouse skin to heat, the effect was dependent on the light dose (Figure 2A, 2B)

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Summary

Introduction

Near infrared photoimmunotherapy (NIR-PIT) is a newly-established cancer therapy utilizing an antibodyphotoabsorber conjugate (APC), which binds to antigens expressed on the cellular membrane of cancer cells. NIR-PIT has entered clinical testing using the anti epidermal growth factor receptor (EGFR) antibody, cetuximab, and the photoabsorber, IR700. This Phase 1 and 2 trial in patients with recurrent inoperable head and neck cancer of NIR-PIT was approved by the US Food and Drug Administration (FDA) in April 2015, and is currently open (https://clinicaltrials.gov/ct2/show/ NCT02422979). Appropriate NIR dose varies with tumor cell type, size, and light source, etc., NIR-PIT proved effective between a light dose of 10–100 J/cm2 [3,4,5]. The most important determinant of NIR-PIT treatment success was that the tumor received at least a certain threshold of total light regardless of the power density or exposure time of the light source [6]

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