Preclinical Evaluation of Benzoporphyrin Derivative Combined with a Light-Emitting Diode Array for Photodynamic Therapy of Brain Tumors

Abstract

Objective: The aim of this study was to investigate the second-generation photosensitizer benzoporphyrin derivative (BPD) and a novel light source applicator based on light-emitting diode (LED) technology for photodynamic therapy (PDT) of brain tumors. Methods: We used a canine model to investigate normal brain stem toxicity. Twenty-one canines underwent posterior fossa craniectomies followed by PDT with BPD. These animals were compared to light only and BPD control. In addition, we investigated the ability of BPD and LED to cause inhibition of cell growth in canine glioma and human glioma cell lines, in vitro. The biodistribution of BPD labeled with ¹¹¹In-BPD in mice with subcutaneous and intracerebral gliomas and canines with brain tumors was studied. Results: The in vivo canine study resulted in a maximal tolerated dose of 0.75 mg/kg of BPD and 100 J/cm² of LED light for normal brain tissue. The in vitro study demonstrated 50% growth inhibition for canine and human glioma cell lines of 10 and 4 ng/ml, respectively. The mucine study using ¹¹¹In-BPD showed a tumor to normal tissue ratio of 12:1 for intracerebral tumors and 3.3:1 for subcutaneous tumors. Nuclear scans of canines with brain tumors showed uptake into tumors to be maximal from 3 to 5 h. Conclusion: Our study supports that BPD and LED light sources when used at appropriate drug and light doses limit normal brain tissue toxicity at doses that can cause significant glioma cell toxicity in vitro. In addition, there is higher BPD uptake in brain tumors as compared to normal brain in a mouse glioma model. These findings make BPD a potential new-generation photosensitizer for the treatment of childhood posterior fossa tumors as well as other malignant cerebral pathology.

Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors

“…Novel methods of improving the effectiveness of photodynamic therapy are being tested experimentally. Schmidt et al reported using second-generation photosensitizers like boronated porphyrins [26], which can be activated by light emitting diodes. Other second-generation photosensitizers include meta-tetrahydroxyphenylchlorin and 5-aminolevulinc acid [27,28].…”

How to distinguish elastically scattered light from Stokes shifted light for solid-state lighting?

“…The absorption and emission bands have peaks at 458 nm and 557 nm, respectively, and overlap in the spectral range between k l ¼ 490 nm and k r ¼ 520 nm. As a result, we distinguish three spectral ranges in the visible spectrum where different physical processes are taking place: (1) in the spectral range up to k l ¼ 490 nm, light is partly elastically scattered and partly absorbed. This range has already been studied in Ref.…”

“…Energy efficient generation of white light is attracting much attention in recent years, since it is important for lighting and for medical and biological applications. [1][2][3][4][5][6][7][8][9][10] One of the main directions is the technology of solid-state lighting, [6][7][8]10 that was recognized with the 2014 Nobel Prize in physics. 11 Solid-state lighting provides superior energy efficiency and flexibility in terms of color temperature.…”

Low-cost photodynamic therapy devices for global health settings: Characterization of battery-powered LED performance and smartphone imaging in 3D tumor models

“…With this in mind it is significant to note that the development of high output light-emitting diodes (LEDs) capable of providing exactly the required illumination in a handheld format, powered by only a few volts from standard consumer batteries, suggests the potential for PDT with a low-cost, portable, battery-powered device. Although LED based sources for PDT and other phototherapy treatments have been adopted 4 5 6 7 8 , to the best of the authors knowledge, sources running entirely on battery power with the optimal combination of spectral properties, irradiance and light delivery options for ALA-PDT have not been described. For example, the commercial battery-powered phototherapy device we are aware of, the Warp 10 ® (Quantum Warp Light Devices, Newark, OH), is approved for phototherapy treatment of muscle and joint pain and has been used in treatment of traumatic injury to the central nervous system 9 .…”