Smith Lydia M, Greenwood Hannah E, Tyrrell Will E, Edwards Richard S, de Santis Vittorio, Baark Friedrich, Firth George, Tanc Muhammet, Terry Samantha Y A, Herrmann Anne, Southworth Richard, Witney Timothy H
School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK.
Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Npj Imaging. 2023 Nov 29;1(1):1. doi: 10.1038/s44303-023-00001-3.
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 F-2-fluoro-2-deoxy-D-glucose (F-FDG) and (4S)-4-(3-F-fluoropropyl)-L-glutamate (F-FSPG). The pattern of F-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, F-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.
小鼠模型是放射性示踪剂开发和验证的宝贵工具。然而，它们成本高昂、通量低，并且受到动物福利考量的限制。在此，我们评估了鸡胚绒毛尿囊膜（CAM）作为小鼠的替代物用于临床前癌症成像研究。在CAM上的基质胶中生长的NCI-H460荧光素酶（FLuc）细胞形成了大小可重复的血管化肿瘤，且不影响胚胎活力。通过设计一种简单的血管插管方法，可以在鸡胚内进行动态PET成像，对于F-2-氟-2-脱氧-D-葡萄糖（F-FDG）和（4S）-4-（3-F-氟丙基）-L-谷氨酸（F-FSPG）均产生高肿瘤与背景信号比。F-FDG在鸡胚内和体内的肿瘤摄取模式相似，尽管在60分钟的成像时间过程中，CAM上生长的肿瘤中与肿瘤相关的放射性更高。此外，F-FSPG为鸡胚内对外照射放疗的治疗反应和靶点抑制提供了早期标志物。总体而言，CAM为肿瘤异种移植小鼠模型提供了一种低成本替代方案，这可能会拓宽PET和SPECT成像的应用范围，并在多种应用中具有实用性。
