Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI

Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI
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DOI:
10.1038/nm940
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发表时间:
2003-10-01
期刊:
影响因子:
82.9
通讯作者:
Salomon, Y
Salomon, Y
中科院分区:
医学1区
文献类型:
--
作者:
Gross, S;Gilead, A;Salomon, Y

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用钯-细菌脱镁叶绿酸(TOOKAD)进行的肿瘤的抗血管光动力疗法(PDT)依赖于通过局部产生细胞毒性活性氧来原位光敏化循环药物,这导致快速血管闭塞、停滞、坏死和肿瘤根除。血管内活性氧的产生与O-2的光消耗和顺磁性脱氧血红蛋白的随后演变有关。在这项研究中,我们评估使用血氧水平依赖(BOLD)对比磁共振成像(MRI)的PDT疗效的实时监测。使用实体瘤模型,我们表明,TOOKAD-PDT产生明显的衰减(25-40%)的磁共振信号,仅在照明肿瘤部位。这种现象是独立的,虽然增强,随后的变化,血流。这些结果通过免疫组织化学和活体显微镜进行了验证。光敏BOLD对比MRI的概念可能在交互式引导和监测抗血管癌症治疗、黄斑变性PDT治疗、介入心脏病学和可能的其他生物医学学科中具有术中应用。
Antivascular photodynamic therapy (PDT) of tumors with palladium-bacteriopheophorbide (TOOKAD) relies on in situ photosensitization of the circulating drug by local generation of cytotoxic reactive oxygen species, which leads to rapid vascular occlusion, stasis, necrosis and tumor eradication. Intravascular production of reactive oxygen species is associated with photoconsumption of O-2 and consequent evolution of paramagnetic deoxyhemoglobin. In this study we evaluate the use of blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for real-time monitoring of PDT efficacy. Using a solid tumor model, we show that TOOKAD-PDT generates appreciable attenuation (25-40%) of the magnetic resonance signal, solely at the illuminated tumor site. This phenomenon is independent of, though augmented by, ensuing changes in blood flow. These results were validated by immunohistochemistry and intravital microscopy. The concept of photosensitized BOLD-contrast MRI may have intraoperative applications in interactive guidance and monitoring of antivascular cancer therapy, PDT treatment of macular degeneration, interventional cardiology and possibly other biomedical disciplines.