Jingjing Shi et al., Preprint, 2021
Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignant diseases among the population in East and Southeast Asia. In order to enable rapid translation of novel cancer drugs from discovery to clinical trial evaluation, the potential of microPET/MR in small animal imaging is of interest for early in vivo testing of these drugs and for performing co-clinical trials. To better understand the underlying pathogenesis of the disease as well as to develop novel treatment strategies, patient-derived xenografts (PDXs) have been used as important models in pre-clinical studies. In NPC research, XenoC15 and XenoC17 represent the most widely used PDXs and the other two available PDXs are Xeno2117 and Xeno666. These have been passaged for over 25 years and are expected to have already lost their original genetic and pathological properties. Among the conventional NPC cell lines that have been available in the past decade, only C666-1 is able to be more representative of clinical NPC. In recent years, several new NPC xenografts and cell lines were established for investigation: C17, Xeno76, Xeno23, NPC43; but the longitudinal growth pattern and the metabolic characteristics of them still remain unknown.
The aim of the present study was to longitudinally evaluate the tumour growth and metabolic activity of two well-established NPC animal models (C666-1, C17) and three novel models (Xeno76, Xeno23 and NPC43) using nanoScan PET/MRI 3T system. Mice injected with 18F-FDG were imaged twice a week for consecutive 3–7 weeks. 18F-FDG uptake was quantified by standardized uptake value (SUV) and presented as SUVmean tumour-to-liver ratio (SUVRmean). SUVRmean and histological characteristics were compared across the five NPC models. Analysis revealed variable tumour growth and metabolic patterns across different NPC tumour types. C17 has an optimal growth rate and higher tumour metabolic activity compared with C666-1. C666-1 has a fast growth rate but is low in SUVRmean at endpoint due to necrosis as confirmed by hematoxylin & eosin staining. NPC43 and Xeno76 have relatively slow growth rates and are low in SUVRmean, due to severe necrosis. Xeno23 has the slowest growth rate, and a relative high SUVRmean. This study establishes an imaging platform that characterizes the growth and metabolic patterns of different NPC models, and the platform is well able to demonstrate drug treatment outcome supporting its use in novel drug discovery and evaluation for NPC.
Results from nanoScan PET/MRI 3T
Tumour cells were injected subcutaneously into the right loin of each NOD.CB17-Prkdcscid/J mouse (male, 4-5 weeks old, n = 5 for each model). Mice were randomized into drug treatment group (weekly ip injection of 4 mg/kg Cisplatin) or vehicle group when tumours reached 50-100 mm3.
After cancer cells injection or tumour fragment implantation, nanoScan PET/MRI monitoring commenced when the tumour was palpable on each mouse. Mice were fasted overnight with free access to water before nanoScan PET/MRI scans. 9.25 ± 0.37 MBq 18F-FDG was injected via lateral tail vein. Animals were scanned twice a week for consecutive 3-7 weeks. T1 and T2 weighted imaging (T1WI and T2WI) were performed on all the mice for tumour size assessment, A 20-minute static PET scan was performed 60 minutes after injection of radiotracer. For drug treatment assessment, 18F-FDG PET scan was performed pre- and post-treatment for tumour uptake comparison. Images were analysed with InterViewFusion software: Volume of interests (VOIs) of liver and tumour were manually drawn on the images, 18F-FDG uptake was quantified by standardized uptake value (SUV). For comparable analysis, the hepatic 18F-FDG uptake was used as an internal reference background for VOI quantification. The tumour SUVmax and SUVmean were normalized by SUVmean_liver and presented as SUVmax_ratio (SUVRmax) and SUVmean_ratio (SUVRmean).
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