Targeting intracranial patient-derived glioblastoma (GBM) with a NIR-I fluorescent immunoconjugate for facilitating its image-guided resection.
Targeting intracranial patient-derived glioblastoma (GBM) with a NIR-I fluorescent immunoconjugate for facilitating its image-guided resection.
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用NIR-I荧光免疫偶联物靶向颅内患者衍生的胶质母细胞瘤（GBM），以促进其图像引导的切除。
DOI：
10.1039/d0ra07245a
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发表时间：
2020-11-22
期刊：
影响因子：
3.9
通讯作者：
Chin FT
中科院分区：
文献类型：
--
作者：
Hettie KS;Teraphongphom NT;Ertsey RD;Rosenthal EL;Chin FT
多形性胶质母细胞瘤(GBM)是原发脑肿瘤中最具侵袭性的一种类型，具有较高的死亡率，存活率仅为15个月。GBM侵袭性与表皮生长因子受体(EGFR)及其突变体的过度表达有关。用治疗药物靶向GBM是具有挑战性的，因为血脑屏障(BBB)主要允许选定的小分子实体穿过其半渗透屏障。然而，最近的临床前数据表明，大的生物分子，如抗EGFR抗体治疗药物西妥昔单抗，可能能够绕过血脑屏障，尽管它的大小相对巨大。因此，我们着手建立以免疫结合物(cetuximab-IRDye800)形式的EGFR靶向近红外-I(NIR-I)荧光构建物的可行性，通过利用原位小鼠GBM39肿瘤模型进行体内和体外评估，实现低传代患者衍生GBM细胞系(GBM39)的病变脑组织和健康脑组织之间的视觉区分，从而为最终促进其体内荧光引导切除和体外外科手术背部病理证实在临床上建立概念证明。正如预期的那样，在白光照射(WLI)下，我们不能在体外完整切除的全脑组织和切片中区分恶性肿瘤组织和健康组织，因为患病组织和健康组织看起来与肉眼几乎相同。然而，当我们在接受免疫结合物治疗的GBM39肿瘤模型的队列上进行NIR-I荧光成像(FLI)时，我们很容易观察到在体外切除的完整脑组织中的荧光发射平均增加了6倍以上。总而言之，我们为建立诸如西妥昔单抗-IRDye800的NIR-I荧光免疫结合物(治疗药物)可以绕过血脑屏障在视觉上提供GBM39肿瘤组织分化的图像引导手术切除奠定了初步的基础。荧光免疫结合物西妥昔单抗-IRDye800绕过血脑屏障，提供患者来源的GBM39脑瘤组织的可视化，便于其荧光引导切除。
Glioblastoma multiforme (GBM) is the most aggressive form of primary brain tumor type and is associated with a high mortality rate borne out of such affording a survival rate of only 15 months. GBM aggressiveness is associated with the overexpression of epidermal growth factor receptor (EGFR) and its mutants. Targeting GBM with therapeutics is challenging because the blood-brain barrier (BBB) permits primarily select small-molecule entities across its semipermeable blockade. However, recent preclinical data suggest that large biomolecules, such as the anti-EGFR antibody therapeutic, cetuximab, could be capable of bypassing the BBB despite the relative enormity of its size. As such, we set forth to establish the feasibility of utilizing an EGFR-targeting near-infrared-I (NIR-I) fluorescent construct in the form of an immunoconjugate (cetuxmimab-IRDye800) to achieve visual differentiation between diseased brain tissue arising from a low-passage patient-derived GBM cell line (GBM39) and healthy brain tissue via utilizing orthotopic intracranial murine GBM39 tumor models for in vivo and ex vivo evaluation such that by doing so would establish proof of concept for ultimately facilitating its in vivo fluorescence-guided resection and ex vivo surgical back-table pathological confirmation in the clinic. As anticipated, we were not capable of distinguishing between malignant tumor tissue and healthy tissue in resected intact and slices of whole brain ex vivo under white-light illumination (WLI) due to both the diseased tissue and healthy tissue appearing virtually identical to the unaided eye. However, we readily observed over an average 6-fold enhancement in the fluorescence emission in the resected intact whole brain ex vivo when performing NIR-I fluorescence imaging (FLI) on the cohort of GBM39 tumor models that were administered the immunoconjugate compared to controls. In all, we laid the initial groundwork for establishing that NIR-I fluorescent immunoconjugates (theranostics) such as cetuximab–IRDye800 can bypass the BBB to visually afford GBM39 tumor tissue differentiation for its image-guided surgical removal. Fluorescent immunoconjugate cetuximab-IRDye800 bypasses the blood-brain-barrier to afford visualization of patient-derived GBM39 brain tumor tissue for facilitating its fluorescence-guided resection.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
21.1
作者：
Shergalis A;Bankhead A 3rd;Luesakul U;Muangsin N;Neamati N
通讯作者：
Neamati N
荧光引导的手术和实时导航 - 一种新的尖端。
DOI：
10.1038/nrc3566
发表时间：
2013-09
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Judy RP;Keating JJ;DeJesus EM;Jiang JX;Okusanya OT;Nie S;Holt DE;Arlauckas SP;Low PS;Delikatny EJ;Singhal S
通讯作者：
Singhal S
影响因子：
7.2
作者：
Zong, Hui;Parada, Luis F.;Baker, Suzanne J.
通讯作者：
Baker, Suzanne J.