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Evaluation of 2-Deoxy-2-[ super(18)F]Fluoro-D-glucose- and 3'-Deoxy-3'-[ super(18)F]Fluorothy midine-Positron Emission Tomography as Biomarkers of Therapy Response in Platinum-Resistant Ovarian Cancer
Ist Teil von
Molecular imaging and biology, 2012-12, Vol.14 (6), p.753-761
Erscheinungsjahr
2012
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
Purpose: We evaluated whether 2-deoxy-2-[ super(18)F]fluoro-D-glucose ([ super(18)F]FDG) and 3'-deoxy-3'-[ super(18)F]fluorothy midine ([ super(18)F]FLT) positron emission tomography (PET) could be used as imaging biomarkers of platinum resensitization in ovarian cancer. Procedures: Paired platinum-sensitive and platinum-resistant ovarian cancer cells from the same patient, PEO1 and PEO4, grown as tumor xenografts in nude mice, were assessed by PET. Results: The AKT inhibitor, API-2, resensitized platinum-resistant PEO4 tumors to cisplatin, leading to a markedly lower Ki67 labeling index (p less than or equal to 0.006, n=6 per group). [ super(18)F]FDG-PET and [ super(18)F]FLT-PET imaging variables were lower after combination treatment compared with vehicle treatment (p less than or equal to 0.006, n=6 per group). No changes were seen with either drug alone. PRAS40 phosphorylation status was a sensitive biochemical marker of pathway inhibition, whereas reductions thymidine kinase 1 expression defined the [ super(18)F]FLT response. Conclusions: Therapeutic inhibition of AKT activation in acquired platinum-resistant disease can be imaged noninvasively by [ super(18)F]FDG-PET and [ super(18)F]FLT-PET warranting further assessment.