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Pc 4 photodynamic therapy of U87-derived human glioma in the nude rat

✍ Scribed by John E. George III; Yusra Ahmad; Davood Varghai; Xiaolin Li; Jeffrey Berlin; David Jackowe; Marc Jungermann; Michael S. Wolfe; Lothar Lilge; Ali Totonchi; Rachel L. Morris; Allyn Peterson; W. David Lust; Malcolm E. Kenney; Charles L. Hoppel; Jiayang Sun; Nancy L. Oleinick; David Dean


Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
200 KB
Volume
36
Category
Article
ISSN
0196-8092

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✦ Synopsis


Abstract

Background and Objectives

As a potential therapy for malignant glioma, we tested the phthalocyanine photosensitizer Pc 4 for: (1) rapid clearance from the vasculature, (2) specificity for glioma, and (3) tumoricidal photosensitizing capability.

Study Design/Materials and Methods

Parenchymal injection of U87 cells into athymic rat brains (N = 100) was followed after 12 days by tail vein injection of 0.5 mg/kg Pc 4. After 1 day, the tumor was illuminated with either 5 (N = 11) or 30 (N = 16) J/cm^2^ red light at 672 nm. Sacrifice was 1 day later. The brains from these 27 animals underwent H&E (necrosis) and TUNEL assay (apoptosis) histology. Pc 4 concentration of explanted brains and tumors (N = 16), and all blood samples (N = 52) were determined by HPLC‐MS 1 day post Pc 4 administration.

Results

Tumor‐specific apoptosis was almost uniformly seen; however, necrosis was found mostly in the high‐light‐dose group. Pc 4 concentration in bulk tumor averaged 3.8 times greater than in normal brain.

Conclusions

These results warrant expanding this pre‐clinical study to seek effective baseline Pc 4 drug‐ and light‐doses and infusion‐to‐photoirradiation timing that would be necessary for a Pc 4‐mediated PDT clinical trial for glioma patients. Lasers Surg. Med. 36:383–389, 2005. © 2005 Wiley‐Liss, Inc.


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