Selective tumor kill of cerebral glioma by photodynamic therapy using a boronated porphyrin photosensitizer

被引:63
作者
Hill, JS
Kahl, SB
Stylli, SS
Nakamura, Y
Koo, MS
Kaye, AH
机构
[1] UNIV MELBOURNE, ROYAL MELBOURNE HOSP, MELBOURNE NEUROSCI CTR, DEPT NEUROSURG, MELBOURNE, VIC 3050, AUSTRALIA
[2] UNIV CALIF SAN FRANCISCO, SCH PHARM, DEPT PHARMACEUT CHEM, SAN FRANCISCO, CA 94143 USA
关键词
brain tumor; hematoporphyrin; boron; neutron capture; phototherapy;
D O I
10.1073/pnas.92.26.12126
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Iii 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 vice, 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.
引用
收藏
页码:12126 / 12130
页数:5
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