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


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.
George
John E
JE
Department of Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
Ahmad
Yusra
Y
Varghai
Davood
D
Li
Xiaolin
X
Berlin
Jeffrey
J
Jackowe
David
D
Jungermann
Marc
M
Wolfe
Michael S
MS
Lilge
Lothar
L
Totonchi
Ali
A
Morris
Rachel L
RL
Peterson
Allyn
A
Lust
W David
WD
Kenney
Malcolm E
ME
Hoppel
Charles L
CL
Sun
Jiayang
J
Oleinick
Nancy L
NL
Dean
David
D
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007275:Injections, Intravenous; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D011923:Rats, Nude
D007211:Indoles; D017319:Photosensitizing Agents; C107448:phthalocyanine Pc 4