Longitudinal evaluation of five nasopharyngeal carcinoma animal models on the microPET/MR platform

Eur J Nucl Med Mol Imaging. 2022 Apr;49(5):1497-1507. doi: 10.1007/s00259-021-05633-4. Epub 2021 Dec 4.

Abstract

Purpose: We longitudinally evaluated the tumour growth and metabolic activity of three nasopharyngeal carcinoma (NPC) cell line models (C666-1, C17 and NPC43) and two xenograft models (Xeno76 and Xeno23) using a micropositron emission tomography and magnetic resonance (microPET/MR). With a better understanding of the interplay between tumour growth and metabolic characteristics of these NPC models, we aim to provide insights for the selection of appropriate NPC cell line/xenograft models to assist novel drug discovery and evaluation.

Methods: Mice were imaged by 18F-deoxyglucose ([18F]FDG) microPET/MR 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). Longitudinal tumour growth patterns and metabolic patterns were recorded. SUVRmean and histological characteristics were compared across the five NPC models. Cisplatin was administrated to one selected optimal tumour model, C17, to evaluate our imaging platform.

Results: We found 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 H&E. 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. Cisplatin showed the expected therapeutic effect in the C17 model in marked reduction of tumour size and metabolism.

Conclusion: Our 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.

Keywords: Nasopharyngeal carcinoma; Necrosis; Patient-derived xenografts; Tumour growth pattern; [18F]FDG; microPET/MR.

MeSH terms

  • Animals
  • Carcinoma*
  • Cisplatin
  • Fluorodeoxyglucose F18
  • Humans
  • Mice
  • Models, Animal
  • Nasopharyngeal Carcinoma / diagnostic imaging
  • Nasopharyngeal Neoplasms* / diagnostic imaging
  • Necrosis
  • Positron-Emission Tomography / methods
  • Tomography, X-Ray Computed

Substances

  • Fluorodeoxyglucose F18
  • Cisplatin