Photodynamic effects of SIM01, a new sensitizer, on experimental brain tumors in rats.
BACKGROUND
Glioblastomas are the third most common cause of cancer death in patients between 15 and 35 years old. Literature suggests that PDT could represent a promising treatment, providing that sensitizers could accumulate within the cancer tissues despite the blood-brain barrier.


METHODS
Distribution and PDT effect of SIM01, a promising photosensitizer, have been evaluated on orthotopic C6 tumor model in rats by comparison with HPD and m-THPC. Pharmacokinetics had been analyzed with fluorescence and ROS. Photodynamic treatment was done using a 630-nm light with an energy density of 100 J cm(-2) for HPD and a 652-nm light with an energy density of 20 J cm(-2) for m-THPC and SIM01.


RESULTS
The correlation between fluorescence and ROS dosimetry was found to be excellent. An optimal concentration was found after 12 hours for SIM01 (4 mg/kg), 24 hours for HPD (10 mg/kg), and 48 hours for m-THPC (4 mg/kg). The best normal tissue/cancer ratio of concentration had been found after 12 hours for SIM01 and 48 hours for HPD and m-THPC. Pathological examinations after PDT showed that the criteria for histology of glioblastic origin were absent in SIM01-treated rats 12 hours after injection but were present in 50% of rats treated 24 hours after injection and in all after a 48-hour delay. Mean survival of rats treated 12 or 24 hours after SIM01 injection was significantly improved compared with controls, HPD-, or m-THPC-treated groups. Survival of rats treated 12 or 24 hours after SIM01 injection reached 20 days but decreased for longer delays. On the contrary, survival reached 18 days at the maximum for rats treated 48 hours after m-THPC or HPD injection.


CONCLUSIONS
Our results confirm that PDT is a promising treatment for glioblastomas. SIM01 efficacy is as efficient as m-THPC but with much more favorable pharmacokinetics.
Olivier
David
D
Département Laser, Neurochirurgie, CHU Nantes, 44480 Nantes, France.
Bourré
Ludovic
L
El-Sabbagh
Emad
E
Loussouarn
Delphine
D
Simonneaux
Gérard
G
Valette
François
F
Patrice
Thierry
T
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
C481258:2,3-dihydro-5,15-bis(3,5-dihydroxyphenyl)porphyrin; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species