Dalby Sina, Skallerup Sofie, Baun Christina, Christensen Lene Gaarsmand, Rathe Mathias, Palner Mikael, Husby Steffen, Moeller Jesper Bonnet
Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Front Oncol. 2022 Dec 15;12:1061804. doi: 10.3389/fonc.2022.1061804. eCollection 2022.
A severe side effect of cancer chemotherapy is the development of gastrointestinal mucositis, characterised by mucosal inflammation. We investigated if 2-deoxy-2-[F] fluoro-D-glucose positron emission tomography combined with computed tomography (2-[F]FDG-PET/CT) could visualise gastrointestinal mucositis in mice treated with the chemotherapeutic agent doxorubicin.
In this study, gastrointestinal inflammation was longitudinally evaluated by 2-[F]FDG-PET/CT scans before and 1, 3, 6, and 10 days after treatment with doxorubicin. Doxorubicin-treated mice were compared to saline-treated littermates using the abdominal standard uptake value of 2-[F]FDG corrected for body weight (SUV).
Abdominal SUV was significantly increased on day 1 (p < 0.0001), day 3 (p < 0.0001), and day 6 (p < 0.05) in the doxorubicin-treated group compared to controls. Abdominal SUV returned to baseline levels on day 10. In the doxorubicin group, the largest weight loss was observed on day 3 (control doxorubicin, mean percent of baseline weight: (98.5 ± 3.2% 87.9 ± 4.6%, p < 0.0001). Moreover, in the doxorubicin-treated group, villus lengths were decreased by 23-28% on days 1 and 3 in the small intestine (p < 0.05), and jejunal levels of tumour necrosis factor and interleukin-1β were significantly increased on day 3 (p < 0.05).
Together, these findings indicate that sequential 2-[F]FDG-PET/CT scans can objectively quantify and evaluate the development and resolution of intestinal inflammation over time in a mouse model of doxorubicin-induced mucositis.
癌症化疗的一种严重副作用是胃肠道粘膜炎的发生,其特征为粘膜炎症。我们研究了2-脱氧-2-[F]氟-D-葡萄糖正电子发射断层扫描联合计算机断层扫描(2-[F]FDG-PET/CT)是否能够使接受化疗药物阿霉素治疗的小鼠的胃肠道粘膜炎可视化。
在本研究中,通过2-[F]FDG-PET/CT扫描在阿霉素治疗前以及治疗后1、3、6和10天对胃肠道炎症进行纵向评估。使用经体重校正的2-[F]FDG的腹部标准摄取值(SUV),将接受阿霉素治疗的小鼠与其接受生理盐水治疗的同窝仔鼠进行比较。
与对照组相比,阿霉素治疗组在第1天(p < 0.0001)、第3天(p < 0.0001)和第6天(p < 0.05)腹部SUV显著升高。腹部SUV在第10天恢复到基线水平。在阿霉素组中,第3天观察到最大体重减轻(对照组对阿霉素组,平均基线体重百分比:(98.5 ± 3.2%对87.9 ± 4.6%,p < 0.0001)。此外,在阿霉素治疗组中,小肠在第1天和第3天绒毛长度减少了23 - 28%(p < 0.05),空肠肿瘤坏死因子和白细胞介素-1β水平在第3天显著升高(p < 0.05)。
总之,这些发现表明,连续的2-[F]FDG-PET/CT扫描能够在阿霉素诱导的粘膜炎小鼠模型中随时间客观地量化和评估肠道炎症的发生和消退情况。