Artikel
Microcontroller-based resection cavity implant for the adjuvant treatment of glioblastoma by repetitive photodynamic therapy and ultraviolet light – demonstration of effectivity in vitro and tolerability in vivo
Mikrokontroller-basiertes intrazerebrales Implantat für die adjuvante Glioblastombehandlung mittels repetitiver photodynamischer Therapie und ultravioletter Bestrahlung – Nachweis von Effektivität in vitro und Tolerabilität in vivo
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Veröffentlicht: | 8. Mai 2019 |
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Objective: In order to treat postoperatively remaining glioblastoma (GBM) cells in the area of the resection cavity wall, the authors have developed a fully implantable system for photodynamic therapy (PDT; 405 and 635 nm) and additional ultraviolet (UV; 280 nm) irradiation which consists of a control unit with power supply and an intracerebral implant (equipped with light emitting diodes) to be placed into the tumor resection cavity. Using in vitro human GBM cell culture models, radiation times required to achieve a “complete therapeutic effect” were determined. Next, tolerability of the repetitively activated implant was investigated in a large-animal experiment.
Methods: In in vitro studies, U-87MG as well as low-passage patient-derived primary GBM cells (IRB no. 162/10) were irradiated with the different wavelengths (in the presence of 5-ALA when using PDT). Repetitive PDT or UV irradiation were evaluated in a total of 14 domestic pigs (ASP no. 1331; study group: n=12; control group with inactive implant: n=2). For this purpose, the implant was inserted into an intracerebral cavity that had been created by limited right frontal lobe resection tailored to the dimensions of the implant (i. e., a 12-mm diameter). The control unit with power supply was inserted in the area of the right scapula with subcutaneous tunneling of electric wires. After implantation, repetitive daily irradiation was carried out over a period of 14 days. During this time, continuous video monitoring was applied. Subsequently, the animals were sacrificed and their brains collected for histopathological analysis.
Results: In vitro studies showed strong antiproliferative or lethal effects on GBM cells by implant-delivered PDT or UV irradiation. When repeatedly applying in vitro “therapeutic” radiation times to the living pigs’ brains, excellent tolerability was observed without any behavioral or neurological abnormalities or signs of phototoxicity. There were no cranial complications and two surgical site infections in the area of the scapula that did not require premature termination. Histopathological analysis is pending.
Conclusion: Repetitive daily exposure to intracerebral-implant-delivered PDT or UV irradiation that is lethal to GBM cells in vitro is well-tolerated by domestic pigs over a period of 14 days without evoking behavioral or neurological sequelae. The next step of evaluation will involve the use of orthotopic GBM xenografts.
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