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¹⁸F-FDG and ¹⁸F-FLT uptake profiles for breast cancer cell lines treated with targeted PI3K/Akt/mTOR therapies

Tijdschriftbijdrage - Tijdschriftartikel

Background: To evaluate F-18-fluoro-2-deoxy-glucose (F-18-FDG) and F-18-fluorothymidine (F-18-FLT) as early-response biomarkers for phosphoinositide-3-kinase/Akt/mammalian-target-of-rapamycin (PI3K/Akt/mTOR) inhibition in breast cancer (BC) models.Materials and Methods: Two human epidermal growth factor receptor 2 (HER2)-positive (trastuzumab-sensitive SKBR3; trastuzumab-resistant JIMT1) and one triple-negative BC cell line (MDA-MB-231, trastuzumab, and everolimus resistant) were treated with trastuzumab (HER2 antagonist), PIK90 (PI3K inhibitor), or everolimus (mTOR inhibitor). Radiotracer uptake was measured before, 24, and 72 h after drug exposure and correlated with changes in cell number, glucose transporter 1 (GLUT1), cell cycle phase, and downstream signaling activation.Results: In responsive cells, cell number correlated with F-18-FLT at 24 h and F-18-FDG at 72 h of drug exposure, except in JIMT1 treated with everolimus, where both radiotracers failed to detect response owing to a temporary increase in tracer uptake. This flare can be caused by reflex activation of Akt combined with a hyperactive insulin-like growth factor I receptor (IGF-1R) signaling, resulting in increased trafficking of GLUTs to the cell membrane (F-18-FDG) and enhanced DNA repair (F-18-FLT). In resistant cells, no major changes were observed, although a nonsignificant flair for both tracers was observed in JIMT1 treated with trastuzumab.Conclusion: F-18-FLT positron emission tomography (PET) detects response to PI3K-targeting therapy earlier than F-18-FDG PET in BC cells. However, therapy response can be underestimated after trastuzumab and everolimus owing to negative feedback loop and crosstalk between pathways.
Tijdschrift: Cancer biotherapy and radiopharmaceuticals
ISSN: 1557-8852
Volume: 38
Pagina's: 51 - 61
Jaar van publicatie:2023
Trefwoorden:A1 Journal article
Toegankelijkheid:Closed