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

Abstract

Test the feasibility of an image-based method to identify taxane resistance in mouse bearing triple-negative breast cancer (TNBC) tumor xenografts. 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. 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. Treated and untreated taxane-sensitive and taxane-resistant cell lines have different metabolic properties that could be leveraged before the start of chemotherapy.