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.
Harry T. Whelan, MD
Medical College of Wisconsin, MACC Fund Research Center, 3017
8701 Watertown Plank Road
Milwaukee, WI 53226 (USA)
Tel. +1 414 456 4090, Fax +1 414 456 6538, E-Mail firstname.lastname@example.org
Received: Received: December 11, 1998
Accepted: April 16, 1999
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 5, Number of References : 35
Founded 1985 by E.B. Hendrick and D.H. Reigel; Editor-in-Chief 1992–1996: F.J. Epstein
Official Journal of the American Society of Pediatric Neurosurgeons (ASPN)
Vol. 30, No. 5, Year 1999 (Cover Date: May 1999)
Journal Editor: D.G. McLone, Chicago, Ill.
ISSN: 1016–2291 (print), 1423–0305 (Online)
For additional information: http://www.karger.com/journals/pne
Article / Publication Details
Copyright / Drug Dosage
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.