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

Facchin, Caterina; Pérez-Liva, Mailyn; Garofalakis, Anikitos; Viel, Thomas; Certain, Anaïs; Balvay, Daniel; Yoganathan, Thulaciga; Woszczyk, J; Sousa, Kelly De; Sourdon, Joevin; Provost, Jean; Tanter, Mickaël; Lussey-Lepoutre, Charlotte; Favier, Judith; Tavitian, Bertrand

doi:10.7150/thno.40687

Cited by 12 publications

(17 citation statements)

References 56 publications

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“…Our results highlight the contribution of multi-organ/multi-modality in vivo imaging for a theranostics approach as proposed earlier 53 , 54 . Such approaches demonstrate that sunitinib-induced cardiotoxicity has several origins, involving a minima pressure-overload, the endothelin axis, and a third mechanism or pathway that remains to be determined for late cardiac hypertrophy.…”

Section: Discussionsupporting

confidence: 79%

Sunitinib-induced cardiac hypertrophy and the endothelin axis

Sourdon¹,

Facchin²,

Certain³

et al. 2021

Theranostics

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Anti-angiogenics drugs in clinical use for cancer treatment induce cardiotoxic side effects. The endothelin axis is involved in hypertension and cardiac remodelling, and addition of an endothelin receptor antagonist to the anti-angiogenic sunitinib was shown to reduce cardiotoxicity of sunitinib in mice. Here, we explored further the antidote effect of the endothelin receptor antagonist macitentan in sunitinib-treated animals on cardiac remodeling. Methods: Tumor-bearing mice treated per os daily by sunitinib or vehicle were imaged before and after 1, 3 and 6 weeks of treatment by positron emission tomography using [ 18 F]fluorodeoxyglucose and by echocardiography. Non-tumor-bearing animals were randomly assigned to be treated per os daily by vehicle or sunitinib or macitentan or sunitinib+macitentan, and imaged by echocardiography after 5 weeks. Hearts were harvested for histology and molecular analysis at the end of in vivo exploration. Results: Sunitinib treatment increases left ventricular mass and ejection fraction and induces cardiac fibrosis. Sunitinib also induces an early increase in cardiac uptake of [ 18 F]fluorodeoxyglucose, which is significantly correlated with increased left ventricular mass at the end of treatment. Co-administration of macitentan prevents sunitinib-induced hypertension, increase in ejection fraction and cardiac fibrosis, but fails to prevent increase of the left ventricular mass. Conclusion: Early metabolic changes predict sunitinib-induced cardiac remodeling. Endothelin blockade can prevent some but not all cardiotoxic side-effects of sunitinib, in particular left ventricle hypertrophy that appears to be induced by sunitinib through an endothelin-independent mechanism.

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Section: Discussionsupporting

confidence: 79%

Sunitinib-induced cardiac hypertrophy and the endothelin axis

Sourdon¹,

Facchin²,

Certain³

et al. 2021

Theranostics

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“…Metabolic resistance preceded tumor growth which was evident after four weeks of treatment. This evidence suggests that 18 F-FDG PET could monitor precisely metabolic changes of PGL during an anti-angiogenic treatment and could possibly predict disease progression (60).…”

Section: Discussionmentioning

confidence: 90%

Sunitinib Treatment for Advanced Paraganglioma: Case Report of a Novel SDHD Gene Mutation Variant and Systematic Review of the Literature

et al. 2021

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BackgroundParagangliomas (PGLs) are neuroendocrine neoplasms arising from chromaffin cells of sympathetic or parasympathetic paraganglia. Systemic therapies have been used only in metastatic PGLs. Antiangiogenic agents, such as sunitinib, could be a viable therapeutic choice in the subgroup of patients with SDH-positive PGLs. We describe the case of a man with Familial Paraganglioma Syndrome type 1 (FPGL) related to a novel mutation in SDHD gene treated with sunitinib. Furthermore, we performed a systematic review of the literature aimed to address the following question: is sunitinib treatment effective in patients with advanced/progressive/metastatic PGL?MethodsWe performed a data search using MEDLINE, Cochrane Library, and Scopus between April 2019 and September 2020. We included studies reporting data on clinical or biological characteristics, or clinical outcomes of patients with PGLs treated with sunitinib.ResultsThe search leaded to the selection of 25 publications. Data from case reports and case series showed that disease control rate (DCR = stable disease + partial response + complete response) was achieved in 34.7% of cases under sunitinib treatment. In 39% of patients DCR was followed by progressive disease (PD) or tumor relapse, 26.1% patients showed PD. Data from clinical trials showed that DCR was 83%, and the median progression free survival was 13.4 months.DiscussionData from the present literature review suggested that sunitinib could be a viable therapeutic option in advanced/progressive/metastatic inoperable PGLs. However, further trials on the efficacy of sunitinib in FPGL and sporadic PGL are needed.

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“…The instrument was assembled from an existing pre-clinical PET-CT system and a clinical UUI device, with the addition of a motorized micro-positioner to operate the US probe within the PET/CT field of view. They showed no significant degradation of PET image quality due to the presence of the US probe (Perez-Liva et al, 2018) and demonstrated the feasibility and interest of hybrid PET/CT/UUI for cancer and cardiac multi-parametric 3D imaging in mice and rats (Facchin et al, 2020). They also mentioned the interest of PET and UUI hybridization for functional brain imaging in rodents.…”

Section: Technical Hybridization Of Neuroimaging Techniquesmentioning

confidence: 90%