Dartmouth Medical School, Dartmouth College, Hanover, New Hampshire, USA.
J Neuropathol Exp Neurol. 2012 Sep;71(9):806-13. doi: 10.1097/NEN.0b013e31826775a1.
In recent years, 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence guidance has been used as a surgical adjunct to improve the extent of resection of gliomas. Exogenous administration of ALA before surgery leads to the accumulation of red fluorescent PpIX in tumor tissue that the surgeon can visualize and thereby discriminate between normal and tumor tissue. Selective accumulation of PpIX has been linked to numerous factors, of which blood-brain barrier breakdown has been suggested to be a key factor. To test the hypothesis that PpIX concentration positively correlates with gadolinium (Gd) concentrations, we performed ex vivo measurements of PpIX and of Gd using inductively coupled plasma mass spectrometry, the latter as a quantitative biomarker of blood-brain barrier breakdown; this was corroborated with immunohistochemistry of microvascular density in surgical biopsies of patients undergoing fluorescence-guided surgery for glioma. We found positive correlations between PpIX concentration and Gd concentration (r = 0.58, p < 0.0001) and between PpIX concentration and microvascular density (r = 0.55, p < 0.0001), suggesting a significant, yet limited, association between blood-brain barrier breakdown and ALA-induced PpIX fluorescence. To our knowledge, this is the first time that Gd measurements by inductively coupled plasma mass spectrometry have been used in human gliomas.
近年来，5-氨基酮戊酸（ALA）诱导的原卟啉 IX（PpIX）荧光引导已被用作提高胶质瘤切除范围的手术辅助手段。手术前外源性给予 ALA 会导致红色荧光 PpIX 在肿瘤组织中积累，外科医生可以可视化并因此区分正常组织和肿瘤组织。PpIX 的选择性积累与许多因素有关，其中血脑屏障破坏被认为是一个关键因素。为了测试 PpIX 浓度与钆（Gd）浓度呈正相关的假设，我们使用电感耦合等离子体质谱法（ICP-MS）对 PpIX 和 Gd 进行了离体测量，后者作为血脑屏障破坏的定量生物标志物；这与接受荧光引导手术治疗的胶质瘤患者的手术活检中小血管密度的免疫组织化学相吻合。我们发现 PpIX 浓度与 Gd 浓度之间存在正相关（r = 0.58，p < 0.0001），PpIX 浓度与微血管密度之间也存在正相关（r = 0.55，p < 0.0001），这表明血脑屏障破坏与 ALA 诱导的 PpIX 荧光之间存在显著但有限的关联。据我们所知，这是首次在人类脑胶质瘤中使用电感耦合等离子体质谱法测量 Gd。
