Predicting Schwannoma Growth in a Tumor Model Using Targeted Imaging.

Predicting Schwannoma Growth in a Tumor Model Using Targeted Imaging.
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DOI:
10.1097/mao.0000000000003063
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发表时间:
2021-06-01
影响因子:
2.1
通讯作者:
Walsh, Erika M.
Walsh, Erika M.
中科院分区:
医学2区
文献类型:
--
作者:
Morrison, Daniel R.;Sorace, Anna G.;Hamilton, Ellis;Moore, Lindsay S.;Houson, Hailey A.;Udayakumar, Neha;Ovaitt, Alyssa;Warram, Jason M.;Walsh, Erika M.

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前庭神经鞘瘤(VS)是神经病学临床上常见的一种病理类型。许多患者是通过“等待和扫描”的方法进行观察的。以前为确定未来增长的放射学指标所做的努力都没有成功。利用小鼠皮下肿瘤模型,我们试图确定定向免疫靶点的荧光成像是否可以用来预测神经鞘瘤的生长速度。抗VEGFR2和抗Her2/Neu的单抗与近红外探针(IRDye800)共价连接。免疫缺陷小鼠接受了大鼠来源的雪旺(R3)细胞系的皮下注射。当肿瘤生长明显时,经尾静脉注射抗VEGFR2-IRDye800、抗Her2/Neu-IRDye800或免疫球蛋白G(Isotype)-IRDye800(对照)。这些小鼠在封闭的近红外设备中连续成像。荧光数据分析肿瘤信号,并与肿瘤SIE和生长率相关。荧光肿瘤信号的异质性也被评估。在抗VEGFR2和抗HER2/Neu组中,第1天的平均肿瘤荧光与最终的最大肿瘤体积有很强的相关性(p=0.002,0.001;r2=0.92,0.86)。与第1天最大肿瘤信号量、最大肿瘤体积呈正相关(p=0.003,0.008;r2=0.9,0.91)。对照组无此相关性(p=0.99,0.75;r2=0.0002,0.028)。考虑到VS干预的潜在发病率,对于生长缓慢或停滞的肿瘤患者,观察是一种合适的方法。我们试图在小鼠模型中识别免疫靶点,利用先进的成像技术预测神经鞘瘤的生长。Her2/Neu和VEGFR2都与肿瘤大小和生长速度密切相关,是值得进一步研究的有希望的靶点。
Vestibular schwannoma (VS) is a common pathology encountered in neurotology clinics. Many patients are observed with a “wait and scan” approach. Previous efforts to determine radiographic indicators of future growth have been unsuccessful. Using a mouse subcutaneous tumor model, we seek to determine if fluorescent imaging with directed immunotargets could be used to predict schwannoma growth rate. Anti-VEGFR2 and anti-Her2/Neu monoclonal antibodies were covalently linked to a near-infrared probe (IRDye800). Immunodeficient mice underwent subcutaneous injections with a rat-derived schwann (R3) cell line. When tumor growth was evident, either Anti-VEGFR2-IRDye800, anti-Her2/Neu-IRDye800, or Immunoglobulin G (IgG) Isotype-IRDye800 (control) were injected via tail vein. The mice were serially imaged in a closed field near-IR device. Fluorescent data were analyzed for tumor signal and correlated with tumor sie and growth rate. Heterogeneity of fluorescent tumor signal was also assessed. In both anti-VEGFR2 and anti-Her2/Neu groups, there were strong correlations between day 1 mean tumor fluorescence and eventual maximum tumor volume (p = 0.002, 0.001; r2 = 0.92, 0.86). There was also strong correlation with maximum tumor signal on day 1 and maximum tumor volume (p = 0.003, 0.008; r2 = 0.90, 0.91). There was no such correlation in the control group (p = 0.99, 0.75; r2 =0.0002, 0.028). Given the potential morbidity in VS intervention, observation is an appropriate approach for patients with slow-growing or stagnant tumors. We seek to identify immunotargets in a murine model that show promise in predicting schwannoma growth with advanced imaging techniques. Both Her2/Neu and VEGFR2 correlated strongly wth tumor size and growth rates and are promising targets that merit further investigation.
DOI: 10.1002/jso.24733
发表时间: 2017-12
影响因子: 2.5
作者:
Prince AC;Jani A;Korb M;Tipirneni KE;Kasten BB;Rosenthal EL;Warram JM
通讯作者: Warram JM