Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Oper Neurosurg (Hagerstown). 2019 Jan 1;16(1):59-70. doi: 10.1093/ons/opy034.
Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but gross-total resection is difficult to achieve in all cases. NF adenomas overexpress folate receptor alpha (FRα).
To test the hypothesis that we could target FRα for highly sensitive and specific intraoperative detection of NF adenomas using near-infrared (NIR) imaging.
Fourteen patients with NF pituitary adenoma were infused with the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to-background ratio (SBR) was recorded for each tumor during resection of the adenomas. Extent of surgery was not modified based on the presence or absence of fluorescence. Immunohistochemistry was performed to assess FRα expression in all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to assess residual neoplasm.
Nine adenomas overexpressed FRα and fluoresced with a NIR SBR of 3.2 ± 0.52, whereas the 5 non-FRα-overexpressing adenomas fluoresced with an SBR of 1.5 ± 0.21. Linear regression demonstrated a significant correlation between intraoperative SBR and the FRα expression (P-value < .001). Analysis of 14 margin samples revealed that the surgeon's impression of the tissue had 83% sensitivity, 100% specificity, 100% positive predictive value, and 89% negative predictive value, while NIR fluorescence had 100% for all values. NIR fluorescence accurately predicted postoperative MRI results in 78% of FRα-overexpressing patients.
Preoperative injection of folate-tagged NIR dye provides strong signal and visualization of NF pituitary adenomas. It is 100% sensitive and specific for detecting margin neoplasm and can predict postoperative MRI findings. Our results suggest that NIR fluorescence may be superior to white-light visualization alone and may improve resection rates in NF pituitary adenomas.
手术切除是非功能性（NF）垂体腺瘤的主要治疗方法，但并非所有病例都能实现大体全切除。NF 腺瘤过度表达叶酸受体α（FRα）。
测试我们是否可以使用近红外（NIR）成像靶向 FRα，以实现对 NF 腺瘤的高度敏感和特异性术中检测。
14 例 NF 垂体腺瘤患者术前输注叶酸类似物 NIR 染料 OTL38。在切除腺瘤过程中记录每个肿瘤的近红外荧光信号与背景比（SBR）。手术范围不根据荧光的有无进行修改。对所有标本进行 FRα 表达的免疫组织化学检测。术后行磁共振成像（MRI）评估残留肿瘤。
9 个腺瘤过度表达 FRα，NIR SBR 为 3.2±0.52，而 5 个非 FRα 过度表达的腺瘤 SBR 为 1.5±0.21。线性回归显示术中 SBR 与 FRα 表达之间存在显著相关性（P 值<.001）。对 14 个边缘样本的分析显示，外科医生对组织的印象具有 83%的敏感性、100%的特异性、100%的阳性预测值和 89%的阴性预测值，而 NIR 荧光具有 100%的所有值。NIR 荧光在 78%的 FRα 过度表达患者中准确预测了术后 MRI 结果。
术前注射叶酸标记的 NIR 染料可提供强烈的信号和 NF 垂体腺瘤的可视化。它对检测边缘肿瘤具有 100%的敏感性和特异性，可预测术后 MRI 结果。我们的结果表明，近红外荧光可能优于单独的白光可视化，并可能提高 NF 垂体腺瘤的切除率。
