Preclinical evaluation of benzoporphyrin derivative combined with a light-emitting diode array for photodynamic therapy of brain tumors.

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/cm(2) 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.

Current therapy and new perspectives in the treatment of medulloblastoma.

Medulloblastoma, a malignant tumor arising from the medullary velum, is the most common malignant brain tumor of childhood. Local extension into the cerebellar hemisphere, infiltration of the floor of the fourth ventricle, and seeding into the subarachnoid space are common. Early diagnosis and improved treatment consisting of surgery followed by radiation and chemotherapy for selected high-risk patients has contributed to a dramatic change in survival. This article reviews current treatment strategies and describes new therapies that have the potential to improve the outlook of children with medulloblastoma.

Light-emitting diodes as a light source for intraoperative photodynamic therapy.

The development of more cost-effective light sources for photodynamic therapy of brain tumors would be of benefit for both research and clinical applications. In this study, the use of light-emitting diode arrays for photodynamic therapy of brain tumors with Photofrin porfimer sodium was investigated. An inflatable balloon device with a light-emitting diode (LED) tip was constructed. These LEDs are based on the new semiconductor aluminum gallium arsenide. They can emit broad-spectrum red light at high power levels with a peak wavelength of 677 nm and a bandwidth of 25 nm. The balloon was inflated with 0.1% intralipid, which served as a light-scattering medium. Measurements of light flux at several points showed a high degree of light dispersion. The spectral emission of this probe was then compared with the absorption spectrum of Photofrin. This analysis showed that the light absorbed by Photofrin with the use of the LED source was 27.5% of that absorbed with the use of the monochromatic 630-nm light. Thus, to achieve an energy light dose equivalent to that of a laser light source, the LED light output must be increased by a factor of 3.63. This need for additional energy is the difference between a 630- and 677-nm absorption of Photofrin. Using the LED probe and the laser balloon adapter, a comparison of brain stem toxicity in canines was conducted. LED and laser light showed the same signs of toxicity at equivalent light energy and Photofrin doses. The maximal tolerated dose of Photofrin was 1.6 mg/kg, using 100 J/cm2 of light energy administered by laser or LED. This study concludes that LEDs are a suitable light source for photodynamic therapy of brain tumors with Photofrin. In addition, LEDs have the potential to be highly efficient light sources for second-generation photosensitizers with absorption wavelengths closer to the LED peak emission.

Management strategies and surgical techniques for deep-seated supratentorial arteriovenous malformations.

The therapeutic options for arteriovenous malformations (AVMs) of the thalamus and the basal ganglia have expanded to include preoperative embolization, stereotactic radiation, and microsurgery. Adjuncts to surgery such as stereotactic guidance, electrophysiological monitoring, intraoperative ultrasound, intraoperative angiography, and induced hypotension have significantly reduced postoperative morbidity. We review the management and outcome of 65 consecutive patients who were treated for deep-seated supratentorial vascular malformations; 45 patients (69%) were treated surgically, 10 patients (15%) were treated conservatively, and 10 patients (15%) underwent radiosurgery. This retrospective study (1976-1993) includes 51 AVMs (78%), 14 cavernous angiomas (22%), and 10 associated vascular anomalies (15%). Initially, 59 (91%) of 65 patients presented with hemorrhage; 23 patients (39%) suffered recurrent hemorrhages. Malformations ranged in size from 1 to 7.5 cm (mean, 2.8 cm). AVMs were fed principally by the anterior and posterior choroidal, thalamoperforate, and lenticulostriate arteries. Venous drainage was uniform via the deep venous system. Among 39 patients who underwent surgery for AVMs, 26 (67%) improved, 7 (18%) remained unchanged, 5 (13%) worsened, and 1 (3%) died. Among six patients who underwent surgery for cavernous angiomas, four (66%) improved, one (17%) remained unchanged, and one (17%) worsened. Operative complications included transient neurological deficits in seven patients (16%), permanent neurological deficits in six patients (13%), and new bleeding from residual AVMs in four patients (9%). Among 10 patients treated conservatively, 3 (30%) had repeat hemorrhages, 2 (20%) had progressive neurological deficits, and 1 (10%) died.(ABSTRACT TRUNCATED AT 250 WORDS)