Hill J S, Kahl S B, Stylli S S, Nakamura Y, Koo M S, Kaye A H
Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12126-30. doi: 10.1073/pnas.92.26.12126.
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.
高级别脑胶质瘤多形性胶质母细胞瘤患者的预后较差。原发性肿瘤的中位生存期小于12个月,大多数在原发肿瘤部位复发,这表明需要更积极的局部治疗来根除侵入邻近脑组织的无法切除的肿瘤细胞“巢”。两种有潜力破坏这些细胞的辅助治疗方法是卟啉敏化光动力疗法(PDT)和硼敏化硼中子俘获疗法(BNCT)。用硼化卟啉2,4-(α,β-二羟乙基)去甲卟啉IX四碳硼烷羧酸酯(BOPP)作为光敏剂的能力,在体外使用C6大鼠胶质瘤细胞系进行了研究,并在体内对植入Wistar大鼠后作为脑内肿瘤生长的C6细胞进行了研究。这些研究确定了在体外实现最大细胞杀伤和在体内实现选择性肿瘤杀伤所需的BOPP剂量和光照剂量。数据表明,BOPP在体内的剂量效果比目前临床使用的光敏剂血卟啉衍生物高10倍,这表明BOPP可能有潜力作为一种双功能的PDT/BNCT敏化剂。