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Pc 4 photodynamic therapy of U87 (human glioma) orthotopic tumor in nude rat brain
Author(s): David Dean; John E. George; Yusra Ahmad; Michael S. Wolfe; Lothar Lilge; Rachel L. Morris; Allyn Peterson; W. David Lust; Ali Totonchi; Davood Varghai; Xiaolin Li; Charles L. Hoppel; Jiayang Sun; Nancy L. Oleinick
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Paper Abstract

Introduction: Photodynamic therapy (PDT) for Barrett’s esophagus, advanced esophageal cancer, and both early and late inoperable lung carcinoma is now FDA-approved using the first generation photosensitizer PhotofrinTM (Axcan Pharma, Birmingham, AL). Photofrin-mediated PDT of glioma is now in Phase III clinical trials. A variety of second generation photosensitizers have been developed to provide improved: (1) specificity for the target tissue, (2) tumoricidal capability, and (3) rapid clearance the vascular compartment, skin, and eyes. The phthalocyanine Pc 4 is a second generation photosensitizer that is in early phase I clinical trials for skin cancer. We have undertaken a preclinical study that seeks to determine if Pc 4-mediated PDT can be of benefit for the intra-operative localization and treatment of glioma. Methods: Using a stereotactic frame, 250,000 U87 cells were injected via Hamilton syringe through a craniotomy, and the dura, 1-2 mm below the cortical surface of nude (athymic) rat brains (N=91). The craniotomy was filled with a piece of surgical PVC and the scalp closed. After two weeks of tumor growth, the animals received 0.5 mg/kg Pc 4 via tail vein injection. One day later the scalp was re-incised, and the PVC removed. The tumor was then illuminated with either 5 or 30 Joule/cm2 of 672-nm light from a diode laser at 50 mW/cm2. The animals were sacrificed one day later and the brain was cold-perfused with formaldehyde. Two thirds of the explanted brains are now being histologically surveyed for necrosis after staining with hematoxylin and eosin and for apoptosis via immunohistochemistry (i.e., TUNEL assay). The other third were analyzed by HPLC-mass spectrometry for the presence of drug in tumor, normal brain, and plasma at sacrifice. Initial histological results show PDT-induced apoptosis and necrosis confined to the growing (live) portion of the tumor. Preliminary analysis shows an average selectivity of Pc 4 uptake in the bulk tumor to be 3.8 times greater than in normal brain tissue. Discussion: The observed specificity and tumoricidal activity of Pc 4 warrants further preclinical studies to determine the preferred Pc 4 drug and light dose for future glioma patient clinical trials.

Paper Details

Date Published: 25 April 2005
PDF: 17 pages
Proc. SPIE 5686, Photonic Therapeutics and Diagnostics, (25 April 2005); doi: 10.1117/12.591213
Show Author Affiliations
David Dean, Case Western Reserve Univ. (United States)
John E. George, Case Western Reserve Univ. (United States)
Yusra Ahmad, Case Western Reserve Univ. (United States)
Michael S. Wolfe, Case Western Reserve Univ. (United States)
Lothar Lilge, Univ. of Toronto (Canada)
Rachel L. Morris, Case Western Reserve Univ. (United States)
Allyn Peterson, Case Western Reserve Univ. (United States)
W. David Lust, Case Western Reserve Univ. (United States)
Ali Totonchi, Case Western Reserve Univ. (United States)
Davood Varghai, Case Western Reserve Univ. (United States)
Xiaolin Li, Case Western Reserve Univ. (United States)
Charles L. Hoppel, Case Western Reserve Univ. (United States)
Jiayang Sun, Case Western Reserve Univ. (United States)
Nancy L. Oleinick, Case Western Reserve Univ. (United States)


Published in SPIE Proceedings Vol. 5686:
Photonic Therapeutics and Diagnostics
Brian Jet-Fei Wong; Eugene A. Trowers; Werner T. W. de Riese; Kenton W. Gregory; Abraham Katzir; Lawrence S. Bass; Karen M. McNally-Heintzelman; Nikiforos Kollias; Reza S. Malek; Henry Hirschberg; Steen J. Madsen; Kenneth Eugene Bartels; Lloyd P. Tate, Editor(s)

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