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

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.

• Authors: John E George 3rd, 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
• Journal: Lasers in surgery and medicine (Lasers Surg Med) Vol. 36 Issue 5 Pg. 383-9 (Jun 2005) ISSN: 0196-8092 [Print] United States
• PMID: 15965990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright 2005 Wiley-Liss, Inc.

Chemical References

• Indoles
• Photosensitizing Agents
• phthalocyanine Pc 4

Topics

• Animals
• Brain Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Glioma (drug therapy, metabolism, pathology)
• Humans
• Indoles (administration & dosage, pharmacokinetics, therapeutic use)
• Injections, Intravenous
• Photochemotherapy
• Photosensitizing Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Rats
• Rats, Nude