Noninvasive Ultra Low Intensity Light Photodynamic Treatment of Glioblastoma with Drug Augmentation: LoGlo PDT Regimen

This paper presents the basis for LoGlo PDT, a new treatment for glioblastoma. Glioblastoma is currently treated with maximal safe resection, temozolomide, and ionizing irradiation. Mortality in 2024 remains over 80% within several years from diagnosis. Oral 5-aminolevulinic acid (5-ALA) is an FDA/EMA approved drug that is selectively taken up by malignant cells, including by glioblastoma. In photodynamic treatment of glioblastoma, intense intraoperative light causes glioblastoma tissue that has taken up 5-ALA to generate cytotoxic reactive oxygen species. The requirement for intense light flux has restricted photodynamic treatment to a single one-hour intraoperative session. We analyze here published data showing that external light, illuminating the entire intact scalp, can attain low μW/cm² flux several cm into intact brain that would be sufficient to mediate 5-ALA photodynamic treatment of glioblastoma if the light and 5-ALA are delivered continuously over 24 h. At the core of LoGlo PDT regimen is the dataset showing that, for a given fluence, as the duration of PDT light delivery goes down, light intensity (flux) delivered must go up to achieve the same glioblastoma cell cytotoxicity as would a weaker light (lower flux) delivered over a longer time. Thus, a repetitive, noninvasive PDT of glioblastoma using an external light source may be possible. We analyze 5-ALA cellular physiology to show that three non-oncology drugs, ciprofloxacin, deferiprone, and telmisartan, can be repurposed to increase light energy capture after 5-ALA, thereby increasing photodynamic treatment's glioblastoma cell cytotoxicity. The LoGlo PDT approach uses both drug augmentation and prolonged ultra-low noninvasive transcranial light delivery for a repetitive, noninvasive 5-ALA photodynamic treatment of glioblastoma.