Utility of [18 F]FLT-PET to assess treatment response in trastuzumab-resistant and trastuzumab-sensitive HER2-overexpressing human breast cancer xenografts.

Whisenant JG, McIntyre JO, Peterson TE, Kang H, Sánchez V, Manning HC, Arteaga CL, Yankeelov TE
Mol Imaging Biol. 2015 17 (1): 119-28

PMID: 25034624 · PMCID: PMC4311727 · DOI:10.1007/s11307-014-0770-z

PURPOSE - The objective of this study was to evaluate 3'-deoxy-3'-[(18) F]fluorothymidine ([(18) F]FLT) positron emission tomography (PET) as an early marker of trastuzumab response in HER2-overexpressing xenografts.

PROCEDURES - Tumor-to-muscle ratios were compared between both trastuzumab-sensitive and trastuzumab-resistant cohorts prior to and after one and two treatments.

RESULTS - A significant difference (P = 0.03) was observed between treated and control trastuzumab-sensitive xenografts after one treatment, which preceded between-group differences in tumor volume. Reduced Ki67 (P = 0.02) and thymidine kinase 1 (TK1) (P = 0.35) immunoreactivity was observed in the treated xenografts. No significant differences in volume, tumor-to-muscle ratio, or immunoreactivity were observed between treated and control trastuzumab-resistant cohorts. A significant difference (P = 0.02) in tumor-to-muscle ratio was observed between trastuzumab-sensitive and trastuzumab-resistant cohorts after two treatments; however, tumor volumes were also different (P = 0.04). Ki67 (P = 0.04) and TK1 (P = 0.24) immunoreactivity was ~50 % less in trastuzumab-sensitive xenografts.

CONCLUSIONS - [(18) F]FLT-PET provided early response assessment in trastuzumab-sensitive xenografts but only differentiated between trastuzumab-resistant and trastuzumab-sensitive xenografts concurrent with differences in tumor size.

MeSH Terms (16)

Animals Antibodies, Monoclonal, Humanized Breast Neoplasms Dideoxynucleosides Drug Design Drug Resistance, Neoplasm Female Humans Immunohistochemistry Ki-67 Antigen Mice Neoplasm Transplantation Positron-Emission Tomography Receptor, ErbB-2 Trastuzumab Xenograft Model Antitumor Assays

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