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Proceedings Paper

A rationale for treating leg length discrepancy using photodynamic therapy
Author(s): Stuart K. Bisland; Crystal Johnson; Mohammed Diab M.D.; Brian C. Wilson
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Paper Abstract

This study investigates the use of photodynamic therapy (PDT) in regulating bone development with a view to its potential role in treating Juvenile leg length discrepancy (LLD). Transgenic mice expressing the luciferase firefly gene upon activation of a promoter sequence specific to the vascular endothelial growth factor (VEGF) gene were subject to benzoporphyrin derivative monoacid (BPD-MA)-mediated PDT in the right, tibial epiphyseal growth plate at the age of 3 weeks. BPD-MA was administered intracardially (2mg/kg) followed 10 mins later by a laser light (690 +/- 5 nm) at a range of doses (5-27J, 50 mW output) delivered either as a single or repeat regimen (x2-3). Contra-lateral legs served as no-light controls. Further controls included animals that received light treatment in the absence of photosensitizer or no treatment. Mice were imaged for VEGF related bioluminescence (photons/sec/steradian) at t= 0, 24, 48, 72 h and 1-4 weeks post PDT. FaxitronTM x-ray images provided accurate assessment of bone morphometry. Upon sacrifice, the tibia and femur of the treated and untreated limbs were harvested, imaged and measured again and prepared for histology. A number of animals were sacrificed at 24 h post PDT to allow immunohistochemical staining for CD31, VEGF and hypoxia-inducible factor (HIF-1 alpha) within the bone. PDT-treated (10 J, x2) mice displayed enhanced bioluminescence at the treatment site (and ear nick) for up to 4 weeks post treatment while control mice were bioluminescent at the ear-nick site only. Repeat regimens provided greater shortening of the limb than the corresponding single treatment. PDT-treated limbs were shorter by 3-4 mm on average as compared to the contra lateral and light only controls (10 J, x2). Immunohistochemistry confirmed the enhanced expression VEGF and CD31 at 4 weeks post-treatment although no increase in HIF-1α was evident at either 24 h or 4 weeks post PDT treatment. Results confirm the utility of PDT to provide localized effects on bone development that may be applicable to other related skeletal deformities.

Paper Details

Date Published: 13 October 2005
PDF: 9 pages
Proc. SPIE 5969, Photonic Applications in Biosensing and Imaging, 596916 (13 October 2005); doi: 10.1117/12.628156
Show Author Affiliations
Stuart K. Bisland, Princess Margaret Hospital/Univ. Health Network (Canada)
Crystal Johnson, Princess Margaret Hospital/Univ. Health Network (Canada)
Mohammed Diab M.D., Univ. of California/San Francisco (United States)
Brian C. Wilson, Princess Margaret Hospital/Univ. Health Network (Canada)

Published in SPIE Proceedings Vol. 5969:
Photonic Applications in Biosensing and Imaging
Brian C. Wilson; Richard I. Hornsey; Warren C. W. Chan; Ulrich J. Krull; Robert A. Weersink; Kui Yu, Editor(s)

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