Photodynamic Therapy For Benign Cutaneous Neurofibromas Using Aminolevulinic Acid Topical Application And 633 Nm Red Light Illumination
PHOTOBIOMODULATION PHOTOMEDICINE AND LASER SURGERY(2021)
摘要
Background: Neurofibromatosis type 1 (NF1) has no current effective treatments beyond surgery. Topical photodynamic therapy (PDT) has the potential to provide a less invasive treatment modality.Objective: Based on murine data, we hypothesized PDT could be used for the treatment of cutaneous neurofibromas (cNF).Methods and results: We conducted a phase I trial to examine absorption and conversion of topical aminolevulinic acid (ALA) in cNF and determine safety in a dose escalation study. ALA or control vehicle was applied to neurofibromas through microneedle-assisted delivery (n = 4) and excised specimens were examined 24 h later for protoporphyrin IX fluorescence. Fluorescence was detected in the tumors at 304 +/- 94 U/mu m(2), while adjacent paralesional normal skin and vehicle-treated tumors showed no fluorescence (p < 0.0001). Subsequently, neurofibromas (n = 27) were treated with ALA and irradiated with 633 nm red light 18 h later, at escalating dosages of 50 and 100 mJ/cm(2). Maximum tolerable dose was established at 100 mJ/cm(2). Light microscopy study of tumors biopsied 48 h after PDT (ALA n = 14 and vehicle n = 4) showed mixed inflammatory infiltrate in the ALA, but not in the vehicle-treated tumors or perilesional normal skin. TUNEL evaluation showed 42.5 +/- 19.9 apoptotic cells per visual field for ALA-treated and 1.1 +/- 1.4 for vehicle-treated tumors (p = 0.002).Conclusions: In the first reported clinical trial of PDT for NF1, PDT targeted neurofibromas specifically, and may offer a normal tissue-sparing treatment modality in the future.This study is registered at Clintrials.gov (NCT01682811).
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关键词
photodynamic therapy (PDT), neurofibromatosis, NF1, ALA, aminolevulinic acid
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