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.


CONCLUSIONS
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.
Schmidt
M H
MH
Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Reichert
K W
KW
Ozker
K
K
Meyer
G A
GA
Donohoe
D L
DL
Bajic
D M
DM
Whelan
N T
NT
Whelan
H T
HT
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use; D004285:Dogs; D005909:Glioblastoma / Q000188:drug therapy; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008027:Light; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D017323:Dihematoporphyrin Ether