Interstitial near-infrared photoimmunotherapy: effective treatment areas and light doses needed for use with fiber optic diffusers

Abstract

Near-infrared photoimmunotherapy (NIR-PIT), a promising cancer therapy utilizing an antibody-photoabsorber conjugate (APC) and NIR light, which induces rapid necrotic cell death only in APC-bound cells. Effective NIR-PIT in mouse models has been achieved using superficial light illumination (SLI) with light emitting diodes (LEDs) or lasers, but in the clinical setting, fiber optic diffusers have been employed to deliver light to deeper tumors. However, the performance of NIR light in tissue delivered by fiber optic diffusers is poorly understood. Here, we investigated NIR-PIT using a cylindrical fiber optic diffuser in a mouse model of A431 tumors. NIR-PIT with 100 J/cm, the same light dose used in clinical trials of NIR-PIT, was applied after insertion of the diffuser within the tumor bed, and then both bioluminescence and fluorescence imaging were analyzed to assess the therapeutic efficacy. The diffuser can deliver adequate NIR light dose for effective NIR-PIT to the A431 tumor at a distance of approximately 1 cm around the light source at 100 J/cm. At 50 J/cm NIR light effective NIR-PIT was reduced to a distance of 5 -7 mm diameter around the light source. These results indicate that the energy of interstitial light (measured in Joules/cm) administered via a fiber diffuser determines the depth of effective NIR-PIT around the diffuser and determines the spacing at which such diffusers should be placed to entirely cover the tumor. Thermal measurements demonstrate that interstitial light for NIR-PIT does not cause damage to the skin overlying the diffuser.

Near Infrared Photo‐Antimicrobial Targeting Therapy for Candida albicans

“…Devices such as optic fiber for NIR irradiating inside the body have been reported. [37][38][39] The antibody is administered externally, orally, by enema, or by intravenous administration, and then NIR irradiation is applied to any site. Therapeutic applications for skin diseases such as ringworm, oral diseases, gastrointestinal infections such as H. pylori, and abscesses are considered.…”

Near-Infrared Photoimmunotherapy Using a Small Protein Mimetic for HER2-Overexpressing Breast Cancer

“…Taken together, HER2 Affibody–IR700Dye conjugate represents an approximately designed therapeutic agent with specific characteristics for NIR-PIT against HER2-overexpressing cancer. When NIR-PIT by the HER2 Affibody–IR700Dye conjugate is contemplated for brain metastases of HER2-overexpressing breast cancer, HER2 status can be examined by imaging [18,28], and NIR light can be irradiated directly during surgery or delivered by an optical fiber diffuser providing the NIR light directly to the tumor [29,30]. 36.2% brain metastases from breast cancer patients overexpressed HER2, and the brain metastases indicated an enrichment in the frequency of tumor HER2 overexpression at this metastatic site [10,31,32].…”

Targeted Photodynamic Therapy: A Novel Approach to Abolition of Human Cancer Stem Cells

“…Another form of ADP is Near Infrared-Photoimmunotherapy (NIR-PIT), which is cancer therapy utilizing an antibody-photoabsorber conjugate (APC) and specifically near infrared light (NIR-light) to activate the PS. The significance of using a PS that is activated by NIR is the properties of the light being harmless to surrounding normal tissue and its penetration depth of 1-2 cm, making it specifically useful on surface tumours [38]. This treatment also exploits the overexpression of specific antigens on a variety of cancer cells, such as mesothelin.…”