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Molecular Imaging and Biology, Online First™
Abstract
Purpose
We evaluated whether 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 3′-deoxy-3′-[18F]fluorothymidine ([18F]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 ≤ 0.006, n = 6 per group). [18F]FDG-PET and [18F]FLT-PET imaging variables were lower after combination treatment compared with vehicle treatment (p ≤ 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 [18F]FLT response.
Conclusions
Therapeutic inhibition of AKT activation in acquired platinum-resistant disease can be imaged noninvasively by [18F]FDG-PET and [18F]FLT-PET warranting further assessment.
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