Author:
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.
Abstract
AbstractMouse 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.
Funder
Wellcome Trust
EPSRC Centre for Doctoral Training in Medical Imaging
Engineering and Physical Sciences Research Council
Centre For Medical Engineering, King’s College London
Cancer Research UK
Publisher
Springer Science and Business Media LLC
Reference40 articles.
1. Kerbel, R. S. What is the optimal rodent model for anti-tumor drug testing? Cancer Metastasis Rev. 17, 301–304 (1998).
2. Richmond, A. & Su, Y. Mouse xenograft models vs GEM models for human cancer therapeutics. Dis. Model Mech. 1, 78–82 (2008).
3. Lampreht Tratar, U., Horvat, S. & Cemazar, M. Transgenic mouse models in cancer research. Front. Oncol. 8, 268 (2018).
4. Greenwood, H. E., Nyitrai, Z., Mocsai, G., Hobor, S. & Witney, T. H. High-throughput PET/CT imaging using a multiple-mouse imaging system. J. Nucl. Med. 61, 292–297 (2020).
5. Martin, D. S. et al. Role of murine tumor models in cancer treatment research. Cancer Res. 46, 2189–2192 (1986).