In Vivo PET/CT in a Human Glioblastoma Chicken Chorioallantoic Membrane Model: A New Tool for Oncology and Radiotracer Development

Abstract

For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers, but the growth of tumors on chicken chorioallantoic membrane (CAM) provides a more rapid, low cost, and ethically sustainable alternative. For the first time, to our knowledge, we demonstrate the feasibility of in vivo PET and CT imaging in a U87 glioblastoma tumor model on chicken CAM, with the aim of applying this model for screening of novel PET tracers. Methods: U87 glioblastoma cells were implanted on the CAM at day 11 after fertilization and imaged at day 18. A small-animal imaging cell was used to maintain incubation and allow anesthesia using isoflurane. Radiotracers were injected directly into the exposed CAM vasculature. Sodium 18 F-fluoride was used to validate the imaging protocol, demonstrating that image-degrading motion can be removed with anesthesia. Tumor glucose metabolism was imaged using 18 F-FDG, and tumor protein synthesis was imaged using 2-18 F-fluoro-L-tyrosine. Anatomic images were obtained by contrast-enhanced CT, facilitating clear delineation of the tumor, delineation of tracer uptake in tumor versus embryo, and accurate volume measurements. Results: PET imaging of tumor glucose metabolism and protein synthesis was successfully demonstrated in the CAM U87 glioblastoma model. Catheterization of CAM blood vessels facilitated dynamic imaging of glucose metabolism with 18 F-FDG and demonstrated the ability to study PET tracer uptake over time in individual tumors, and CT imaging improved the accuracy of tumor volume measurements. Conclusion: We describe the novel application of PET/CT in the CAM tumor model, with optimization of typical imaging protocols. PET imaging in this valuable tumor model could prove particularly useful for rapid, high-throughput screening of novel radiotracers. PETi maging has proved an indispensable tool in oncology research and in clinical oncology (1). 18 F-FDG has been widely used to study tumor proliferation and metastasis in vivo, and radiotracers targeting specific proteins expressed on tumor cells are constantly under development (2). In recent years, there has been a substantial growth in the use of combined PET and CT imaging, both in the clinic and for small-animal research. This combination yields functional imaging data with useful anatomic information.For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers. However, despite their wide use in oncology research, mouse models obviously require all usual aspects of animal husbandry, necessitating cost and taking up valuable lab space. In particular, rodent models can be limited in their usefulness by difficulty in obtaining exact measures of tumor progression (such as volume) (3). Ethical issues relating to animal suffering and public opinion are also of increasing concern (4). Clearly, an alternative could be useful.The chicken chorioallantoic membra...

The chicken chorioallantoic membrane model in biology, medicine and bioengineering

“…This research was originally published in JNM. Warnock et al [55]. © by the Society of Nuclear Medicine and Molecular Imaging, Inc.…”

Accessibilome of Human Glioblastoma: Collagen-VI-alpha-1 Is a New Target and a Marker of Poor Outcome

“…We have previously demonstrated the usefulness of the U87 CAM model for early preclinical tumor imaging. 31 Along these lines, we have tested in the present study the ability of anti-COL6A1 antibody to reach the tumor in the U87 CAM-based glioblastoma model. As demonstrated in Figure 5A, U87 tumor grown on CAM is highly angiogenic and features functional vasculature (evidenced by the presence of nucleated chicken red blood cells in the vessel lumen).…”

Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study

“…There is a linear relationship in PET signals between GBM cell number and 18 F-FDG uptake levels by these cells, that is significantly higher in small cell lung cancer with activity [88]. In small animals, 18 F-FDG reaches tumor internalization plateau approximately after 45 min of administration [89,90]. It is possible that the decrease in glucose consumption evidenced in our study is related to decreased nutritional intake due to antiangiogenic effects.…”