The invention of the implantable light irradiating device for photodynamic therapy

Malignant gliomas, particularly glioblastoma, have a poor prognosis, with a median overall survival of approximately 18 months and a 5-year survival rate of less than 10% following current standard treatments (surgery, chemotherapy, and radiotherapy). The intractability of this disease is attributed to the inability to achieve complete surgical resection and the therapeutic resistance of glioma stem cells.
Photodynamic therapy (PDT) is expected to develop as a novel treatment modality that exerts direct cytotoxic effects via reactive radical species generated intracellularly through photodynamic reactions, using photosensitizers that preferentially accumulate in tumor cells.
5-Aminolevulinic acid (ALA), a naturally occurring porphyrin precursor, is endogenously present and is associated with minimal severe side effects.
PDT using talaporfin (TPF-PDT) for malignant glioma has already been approved for clinical use, and ALA-mediated PDT (ALA-PDT) is currently under clinical investigation in Europe. The high tumor selectivity of PDT allows for repeated treatments (metronomic PDT), which may provide greater antitumor effects compared with single-session treatment (Bisland SK et al., Photochem Photobiol., 2004; Yamamoto J et al., Clin Cancer Res., 2006).
Conventional PDT does not utilize ALA and requires high-intensity laser irradiation. This leads to photobleaching induced by high energy exposure, resulting in degradation of the photosensitizer and reduced treatment efficiency.
In contrast, ALA-mediated PDT enables prolonged irradiation at low light intensity. To realize this approach, an implantable light-emitting device placed on the brain surface is required.
Our laboratory is collaborating with a research group led by Shuji Nakamura at the University of California, Santa Barbara—recipient of the 2014 Nobel Prize in Physics—to develop an implantable intracranial light source device that enables repeated PDT for malignant glioma.

The annual incidence of malignant gliomas, particularly glioblastoma, is estimated at approximately 6,000 cases in Japan and around 250,000 cases worldwide. These tumors are highly resistant to current standard therapies, including surgery, chemotherapy, and radiotherapy, and there is a strong unmet need for novel treatment strategies.
In conventional photodynamic therapy, such as talaporfin-mediated PDT (TPF-PDT), photosensitivity is a notable adverse effect. In contrast, ALA-mediated PDT (ALA-PDT) does not induce severe side effects such as photosensitivity.
If the implantable intracranial light-irradiation device developed by our group demonstrates both efficacy and safety, it has the potential for widespread global adoption. The application of this device is not limited to malignant brain tumors. Owing to its sheet-like structure, similar to paper, the device can conform closely to uneven tissue surfaces, enabling its application to cancers in other organs, such as esophageal, lung, colorectal, and prostate cancers.
Furthermore, this device is applicable not only to photodynamic therapy but also to photoimmunotherapy. Given its broad applicability and the large number of potential patients, this technology has the potential to become a high-value medical device in the global market.

This device is designed to be semi-permanently implanted within the resection cavity during craniotomy for brain tumor removal, enabling repeated photodynamic therapy (PDT) sessions during outpatient visits. We aim to obtain insurance coverage for this device as a platform for repeated PDT.
The target indications for insurance coverage are not limited to malignant brain tumors but are also intended to include cancers in other organs. By modifying the embedded LED chips, the device can emit light at different wavelengths, making it applicable not only to PDT but also to photoimmunotherapy, which likewise utilizes light irradiation. Therefore, it has the potential to be covered by insurance for multiple therapeutic modalities.
ALA is already approved as an oral agent for photodynamic diagnosis during surgery. In the future, we aim to establish a treatment approach in which patients take oral ALA, followed by activation of this device for a defined period to perform PDT. Ultimately, our goal is to enable patients to receive treatment at home.