Hill J S, Kahl S B, Kaye A H, Stylli S S, Koo M S, Gonzales M F, Vardaxis N J, Johnson C I
Department of Surgery, University of Melbourne, Victoria, Australia.
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1785-9. doi: 10.1073/pnas.89.5.1785.
The prognosis for patients with high-grade cerebral glioma is poor. Most treatment failures are due to local recurrence of tumor, indicating that a more aggressive local therapy could be beneficial. Adjuvant treatments such as porphyrin-sensitized photodynamic therapy (PDT) or boron neutron capture therapy (BNCT) have the potential to control local recurrence. The selective tumor uptake of a boronated porphyrin was studied in CBA mice bearing an implanted intracerebral glioma. Biopsy samples of tumor, normal brain, and blood were analyzed by a fluorometric assay following intraperitoneal and intravenous administration of boronated protoporphyrin (BOPP). This compound was selectively localized to tumor at ratios as high as 400:1 relative to normal brain. Confocal laser scanning microscopy of glioma cells in vitro and in vivo showed that BOPP was localized within mitochondria and excluded from the nucleus of these cells. This discrete subcellular localization was confirmed by density gradient ultracentrifugation after homogenization of mouse tumor biopsies. The selective discrete localization of these compounds within the tumor suggests that this compound may be used as a dual PDT/BNCT sensitizer.
高级别脑胶质瘤患者的预后较差。大多数治疗失败是由于肿瘤局部复发，这表明更积极的局部治疗可能有益。辅助治疗如卟啉敏化光动力疗法（PDT）或硼中子俘获疗法（BNCT）有可能控制局部复发。在植入脑内胶质瘤的CBA小鼠中研究了硼化卟啉对肿瘤的选择性摄取。在腹腔和静脉注射硼化原卟啉（BOPP）后，通过荧光测定法分析肿瘤、正常脑和血液的活检样本。该化合物相对于正常脑以高达400:1的比例选择性定位于肿瘤。体外和体内胶质瘤细胞的共聚焦激光扫描显微镜显示，BOPP定位于线粒体中，且排除在这些细胞的细胞核之外。在小鼠肿瘤活检样本匀浆后通过密度梯度超速离心证实了这种离散的亚细胞定位。这些化合物在肿瘤内的选择性离散定位表明该化合物可用作双重PDT/BNCT敏化剂。
