Concurrent imaging of vascularization and metabolism in a mouse model of paraganglioma under anti-angiogenic treatment - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Theranostics Année : 2020

Concurrent imaging of vascularization and metabolism in a mouse model of paraganglioma under anti-angiogenic treatment

Thomas Viel
Mickael Tanter

Résumé

Rationale: Deregulation of metabolism and induction of vascularization are major hallmarks of cancer. Using a new multimodal preclinical imaging instrument, we explored a sequence of events leading to sunitinib-induced resistance in a murine model of paraganglioma (PGL) invalidated for the expression of succinate dehydrogenase subunit B (Sdhb-/-). Methods: Two groups of Sdhb-/-tumors bearing mice were treated with sunitinib (6 weeks) or vehicle (3 weeks). Concurrent Positron Emission Tomography (PET) with 2′-deoxy-2′-[ 18 F]fluoro-D-glucose (FDG), Computed Tomography (CT) and Ultrafast Ultrasound Imaging (UUI) imaging sessions were performed once a week and ex vivo samples were analyzed by western blots and histology. Results: PET-CT-UUI enabled to detect a rapid growth of Sdhb-/-tumors with increased glycolysis and vascular development. Sunitinib treatment prevented tumor growth, vessel development and reduced FDG uptake at week 1 and 2 (W1-2). Thereafter, imaging revealed tumor escape from sunitinib treatment: FDG uptake in tumors increased at W3, followed by tumor growth and vessel development at W4-5. Perfused vessels were preferentially distributed in the hypermetabolic regions of the tumors and the perfused volume increased during escape from sunitinib treatment. Finally, initial changes in total lesion glycolysis and maximum vessel length at W1 were predictive of resistance to sunitinib. Conclusion: These results demonstrate an adaptive resistance of Sdhb-/-tumors to six weeks of sunitinib treatment. Early metabolic changes and delayed vessel architecture changes were detectable and predictable in vivo early during anti-angiogenic treatment. Simultaneous metabolic, anatomical and functional imaging can monitor precisely the effects of anti-angiogenic treatment of tumors.
Fichier principal
Vignette du fichier
thnov10p3518.pdf (2.49 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03431298 , version 1 (16-11-2021)

Identifiants

Citer

Caterina Facchin, Mailyn Perez-Liva, Anikitos Garofalakis, Thomas Viel, Anais Certain, et al.. Concurrent imaging of vascularization and metabolism in a mouse model of paraganglioma under anti-angiogenic treatment. Theranostics, 2020, 10, pp.3518 - 3532. ⟨10.7150/thno.40687⟩. ⟨hal-03431298⟩
27 Consultations
23 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More