An in vivo tumour organoid model based on the chick embryonic chorioallantoic membrane mimics key characteristics of the patient tissue: a proof-of-concept study

Author(s): Katarína Benčurová, Loan Tran, Joachim Friske, Kajetana Bevc, Thomas H. Helbich, Marcus Hacker, Michael Bergmann, Markus Zeitlinger, Alexander Haug, Markus Mitterhauser, Gerda Egger, Theresa Balber
Abstract: Background: Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient – in vitro PDOs – in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns. Results: The main liver metastasis of the CRC patient exhibited high 2-[¹⁸F]FDG uptake and moderate and focal [⁶⁸Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[¹⁸F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient’s liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient’s sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [⁶⁸Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [⁶⁸Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking. Conclusions: We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient’s tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [⁶⁸Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[¹⁸F]FDG was avidly taken up in the patient’s liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients. Graphical Abstract: (Figure presented.)
Organisation(s): Joint Applied Medicinal Radiochemistry Facility, Department of Inorganic Chemistry
External organisation(s): Medizinische Universität Wien, Christian Doppler Research Association, Ludwig Boltzmann Intitute Applied Diagnostics
Journal: EJNMMI Research
Volume: 14
ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-024-01151-0
Publication date: 12-2024
Peer reviewed: Yes
Austrian Fields of Science 2012: 302054 Nuclear medicine, 301305 Medical chemistry, 301904 Cancer research
Keywords
ASJC Scopus subject areas: Radiology Nuclear Medicine and imaging
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Portal url: https://ucrisportal.univie.ac.at/en/publications/0b48c83d-82d2-47cc-8db5-6e8844d8c5ca