Selective tumor kill of cerebral glioma by photodynamic therapy using a boronated porphyrin photosensitizer.
The prognosis for patients with the high-grade cerebral glioma glioblastoma multiforme is poor. The median survival for primary tumors is < 12 months, with most recurring at the site of the original tumor, indicating that a more aggressive local therapy is required to eradicate the unresectable "nests" of tumor cells invading into adjacent brain. Two adjuvant therapies with the potential to destroy these cells are porphyrin-sensitized photodynamic therapy (PDT) and boron-sensitized boron neutron capture therapy (BNCT). The ability of a boronated porphyrin, 2,4-(alpha, beta-dihydroxyethyl) deuteroporphyrin IX tetrakiscarborane carboxylate ester (BOPP), to act as a photosensitizing agent was investigated in vitro with the C6 rat glioma cell line and in vivo with C6 cells grown as an intracerebral tumor after implantation into Wistar rats. These studies determined the doses of BOPP and light required to achieve maximal cell kill in vitro and selective tumor kill in vivo. The data show that BOPP is more dose effective in vivo by a factor of 10 than the current clinically used photosensitizer hematoporphyrin derivative and suggest that BOPP may have potential as a dual PDT/BNCT sensitizer.
Hill
J S
JS
Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
Kahl
S B
SB
Stylli
S S
SS
Nakamura
Y
Y
Koo
M S
MS
Kaye
A H
AH
D000818:Animals; D001896:Boron Compounds / Q000627:therapeutic use* / Q000633:toxicity; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003905:Deuteroporphyrins / Q000627:therapeutic use* / Q000633:toxicity; D004307:Dose-Response Relationship, Radiation; D005909:Glioblastoma / Q000188:drug therapy; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D017324:Hematoporphyrin Derivative / Q000627:therapeutic use; D006801:Humans; D007834:Lasers; D008027:Light; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D014407:Tumor Cells, Cultured; D000098851:Carboranes
D001896:Boron Compounds; D003905:Deuteroporphyrins; D017324:Hematoporphyrin Derivative; D017319:Photosensitizing Agents; C080251:2,4-(alpha,beta-dihydroxyethyl)deuteroporphyrin IX tetrakiscarborane carboxylate ester; D000098851:Carboranes