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Evaluation of 2-Deoxy-2-[18F]Fluoro-D-glucose- and 3′-Deoxy-3′-[18F]Fluorothymidine–Positron Emission Tomography as Biomarkers of Therapy Response in Platinum-Resistant Ovarian Cancer

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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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Acknowledgments

The authors thank grant support from Cancer Research UK and Engineering and Physical Sciences Research Council (C2536/A10337), UK Medical Research Council (U1200.005.00001.01) and Ovarian Cancer Action. We would like to thank the Staff at the Biological Imaging Centre at Imperial College for their support.

Potential Conflict of Interest Statement

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Comprehensive Cancer Imaging Centre, Department of Cancer & Surgery, Faculty of Medicine, Imperial College London, Hammersmith Hospital, 240 MRC Cyclotron Building, Du Cane Road, London, W12 0NN, UK

    Meg Perumal & Eric O. Aboagye

  2. Ovarian Cancer Action Research Centre, Department of Cancer & Surgery, Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

    Euan A. Stronach & Hani Gabra

Authors
  1. Meg Perumal
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  2. Euan A. Stronach
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  3. Hani Gabra
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  4. Eric O. Aboagye
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Correspondence to Eric O. Aboagye.

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Perumal, M., Stronach, E.A., Gabra, H. et al. Evaluation of 2-Deoxy-2-[18F]Fluoro-D-glucose- and 3′-Deoxy-3′-[18F]Fluorothymidine–Positron Emission Tomography as Biomarkers of Therapy Response in Platinum-Resistant Ovarian Cancer. Mol Imaging Biol 14, 753–761 (2012). https://doi.org/10.1007/s11307-012-0554-2

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