Detection of metabolic adaptation in a triple-negative breast cancer animal model with [18F]choline-PET imaging as a surrogate for drug resistance

Eur J Nucl Med Mol Imaging. 2024 Apr;51(5):1261-1267. doi: 10.1007/s00259-023-06546-0. Epub 2023 Dec 14.

Abstract

Purpose: Test the feasibility of an image-based method to identify taxane resistance in mouse bearing triple-negative breast cancer (TNBC) tumor xenografts.

Methods: Xenograft tumor-bearing mice from paclitaxel-sensitive and paclitaxel-resistant TNBC cells (MDA-MD-346) were generated by orthotopic injection into female NOD-SCID mice. When tumors reached 100-150 mm3, mice were scanned using [18F]choline PET/CT. Tumors were collected and sliced for autoradiography and immunofluorescence analysis. Quantitative data was analyzed accordingly.

Results: From fifteen mice scanned, five had taxane-sensitive cell line tumors of which two underwent taxol-based treatment. From the remaining 10 mice with taxane-resistant cell line tumors, four underwent taxol-based treatment. Only 13 mice had the tumor sample analyzed histologically. When normalized to the blood pool, both cell lines showed differences in metabolic uptake before and after treatment.

Conclusions: Treated and untreated taxane-sensitive and taxane-resistant cell lines have different metabolic properties that could be leveraged before the start of chemotherapy.

Keywords: Drug resistance; NOD mice; PET/CT; SCID mice; Triple-negative breast neoplasm.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Resistance
  • Female
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Models, Animal
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Positron Emission Tomography Computed Tomography* / methods
  • Positron-Emission Tomography / methods
  • Triple Negative Breast Neoplasms* / diagnostic imaging
  • Triple Negative Breast Neoplasms* / drug therapy
  • Xenograft Model Antitumor Assays

Substances

  • Paclitaxel