Ackerman Shelley E, Wilson Christy M, Kahn Suzana A, Kintzing James R, Jindal Darren A, Cheshier Samuel H, Grant Gerald A, Cochran Jennifer R
Bioengineering, Stanford University.
School of Medicine, Stanford University.
Cureus. 2014;6(9). doi: 10.7759/cureus.207. Epub 2014 Sep 17.
Tumors of the central nervous system are challenging to treat due to the limited effectiveness and associated toxicities of chemotherapy and radiation therapy. For tumors that can be removed surgically, extent of malignant tissue resection has been shown to correlate with disease progression, recurrence, and survival. Thus, improved technologies for real-time brain tumor imaging are critically needed as tools for guided surgical resection. We previously engineered a novel peptide that binds with high affinity and unique specificity to αβ, αβ, and αβ integrins, which are present on tumor cells, and the vasculature of many cancers, including brain tumors. In the current study, we conjugated this engineered peptide to a near infrared fluorescent dye (Alexa Fluor 680), and used the resulting molecular probe for non-invasive whole body imaging of patient-derived medulloblastoma xenograft tumors implanted in the cerebellum of mice. The engineered peptide exhibited robust targeting and illumination of intracranial medulloblastoma following both intravenous and intraperitoneal injection routes. In contrast, a variant of the engineered peptide containing a scrambled integrin-binding sequence did not localize to brain tumors, demonstrating that tumor-targeting is driven by specific integrin interactions. imaging was used to confirm the presence of tumor and molecular probe localization to the cerebellar region. These results warrant further clinical development of the engineered peptide as a tool for image-guided resection of central nervous system tumors.
由于化疗和放射治疗的效果有限以及相关毒性，中枢神经系统肿瘤的治疗具有挑战性。对于可以通过手术切除的肿瘤，恶性组织切除范围已被证明与疾病进展、复发和生存率相关。因此，作为引导手术切除的工具，迫切需要改进的实时脑肿瘤成像技术。我们之前设计了一种新型肽，它能与肿瘤细胞以及包括脑肿瘤在内的许多癌症的脉管系统上存在的αβ、αβ和αβ整合素高亲和力且独特特异性地结合。在当前研究中，我们将这种设计的肽与近红外荧光染料（Alexa Fluor 680）偶联，并使用所得分子探针对植入小鼠小脑的患者来源的髓母细胞瘤异种移植肿瘤进行非侵入性全身成像。在静脉内和腹腔内注射途径后，设计的肽均表现出对颅内髓母细胞瘤的强大靶向和显影作用。相比之下，含有乱序整合素结合序列的设计肽变体未定位到脑肿瘤，这表明肿瘤靶向是由特定的整合素相互作用驱动的。成像用于确认肿瘤的存在以及分子探针在小脑区域的定位。这些结果为将设计的肽作为中枢神经系统肿瘤图像引导切除的工具进行进一步临床开发提供了依据。
