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In vivo monitoring of the therapeutic efficacy of a CXCR1/2 inhibitor with 18F-FDG PET/CT imaging in experimental head and neck carcinoma: A feasibility study
Authors:Christopher Montemagno  Benjamin Serrano  Jérôme Durivault  Valérie Nataf  François Mocquot  Régis Amblard  Valérie Vial  Cyril Ronco  Rachid Benhida  Maeva Dufies  Marc Faraggi  Gilles Pagès
Institution:1. Département de Biologie Médicale, Centre Scientifique de Monaco, Monaco;2. Medical Physics Department, Centre Hospitalier Princesse Grace, Monaco, Monaco;3. Nuclear Medicine Department, Centre Hospitalier Princesse Grace, Monaco, Monaco;4. Institute for Research on Cancer and Aging of Nice, Université Cote D’Azur, CNRS UMR 7284, INSERM U1081, Centre Antoine Lacassagne, 06200, Nice, France;5. Université Côte D''Azur, CNRS, Institut de Chimie de Nice UMR 7272, 06108, Nice, France
Abstract:The chemokine receptors CXCR1/2 play a key role in the aggressiveness of several types of cancers including head and neck squamous cell carcinomas (HNSCCs). In HNSCCs, CXCR1/2 signaling promotes cell proliferation and angiogenesis leading to tumor growth and metastasis. The competitive inhibitor of CXCR1/2, C29, inhibits the growth of experimental HNSCCs in mice. However, a non-invasive tool to monitor treatment response is essential to implement the use of C29 in clinical practices. 18F-FDG PET/CT is a gold-standard tool for the staging and the post-therapy follow-up of HNSCCs patients. Our study aimed to perform the first in vivo monitoring of C29 efficacy by non-invasive 18F-FDG PET/CT imaging. Mice bearing experimental HNSCCs (CAL33) were injected with 18F-FDG (T0) and thereafter treated (n = 7 mice, 9 tumors, 50 mg/kg by gavage) or not (n = 7 mice, 10 tumors) with C29 for 4 consecutive days. Final 18F-FDG-tumor uptake was determined at day 4 (TF). The average relative change (TF-T0) in 18F-FDG tumor uptake was +25.85 ± 10.93 % in the control group vs ?5.72 ± 10.07 % in the C29-treated group (p < 0.01). These results were consistent with the decrease of the tumor burden and with the decrease of tumor proliferating Ki67+ cells. These results paved the way for the use of 18F-FDG to monitor tumor response following C29 treatment.
Keywords:CXCR1/2  HNSCCs  Chemical inhibitor  PET/CT imaging
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