The chicken chorioallantoic membrane as a low-cost, high-throughput model for cancer imaging

Lydia M. Smith, Hannah E. Greenwood, Will E. Tyrrell, Richard S. Edwards, Vittorio de Santis, Friedrich Baark, George Firth, Muhammet Tanc, Samantha Y. A. Terry, Anne Herrmann, Richard Southworth, Timothy H. Witney
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Abstract

Mouse models are invaluable tools for radiotracer development and validation. They are, however, expensive, low throughput, and are constrained by animal welfare considerations. Here, we assessed the chicken chorioallantoic membrane (CAM) as an alternative to mice for preclinical cancer imaging studies. NCI-H460 FLuc cells grown in Matrigel on the CAM formed vascularized tumors of reproducible size without compromising embryo viability. By designing a simple method for vessel cannulation it was possible to perform dynamic PET imaging in ovo, producing high tumor-to-background signal for both 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and (4S)-4-(3-18F-fluoropropyl)-L-glutamate (18F-FSPG). The pattern of 18F-FDG tumor uptake were similar in ovo and in vivo, although tumor-associated radioactivity was higher in the CAM-grown tumors over the 60 min imaging time course. Additionally, 18F-FSPG provided an early marker of both treatment response to external beam radiotherapy and target inhibition in ovo. Overall, the CAM provided a low-cost alternative to tumor xenograft mouse models which may broaden access to PET and SPECT imaging and have utility across multiple applications.

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鸡绒毛膜是一种低成本、高通量的癌症成像模型
小鼠模型是放射性示踪剂开发和验证的宝贵工具。然而,小鼠模型价格昂贵、通量低,而且受到动物福利因素的限制。在这里,我们评估了鸡绒毛膜(CAM)作为小鼠临床前癌症成像研究的替代品。在CAM上的Matrigel中生长的NCI-H460 FLuc细胞形成了大小可重复的血管化肿瘤,而不会影响胚胎的存活率。通过设计一种简单的血管插管方法,可以在胚胎中进行动态 PET 成像,为 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) 和 (4S)-4-(3-18F-fluoropropyl)-L-glutamate (18F-FSPG) 产生较高的肿瘤-背景信号。18F-FDG的肿瘤摄取模式在体内和体外相似,但在60分钟的成像过程中,CAM生长的肿瘤中肿瘤相关放射性更高。此外,18F-FSPG 还是体外放疗反应和体内靶点抑制的早期标记物。总之,CAM 为肿瘤异种移植小鼠模型提供了一种低成本的替代方法,它可以拓宽 PET 和 SPECT 成像的应用范围,并在多种应用中发挥作用。
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