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.

Purpose: We evaluated whether 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine ([(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-res...

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Published in:Molecular Imaging & Biology Vol. 14; no. 6; pp. 753 - 762
Main Authors: Perumal M, Stronach EA, Gabra H, Aboagye EO, Perumal, Meg, Stronach, Euan A, Gabra, Hani, Aboagye, Eric O
Format: research Journal Article
Published: Springer Nature Dec2012
Online Access:View this record in EBSCOhost
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      dt: Dec2012
      vid: 14
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s11307-012-0554-2
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        atl: 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.
      aug:
        au:
          Perumal M
          Stronach EA
          Gabra H
          Aboagye EO
          Perumal, Meg
          Stronach, Euan A
          Gabra, Hani
          Aboagye, Eric O
        affil: 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
      sug:
        subj:
          Deoxyribonucleosides Diagnostic Use
          Drug Resistance, Neoplasm
          Fludeoxyglucose F 18 Diagnostic Use
          Ovarian Neoplasms Radiography
          Platinum Therapeutic Use
          Tomography, Emission-Computed
          Tumor Markers, Biological Metabolism
          Animal Studies
          Blotting, Western
          Cells
          Deoxyribonucleosides Pharmacokinetics
          Female
          Fludeoxyglucose F 18 Pharmacokinetics
          Mice
          Ovarian Neoplasms Drug Therapy
          Platinum Pharmacodynamics
          Sulfonylurea Compounds
          Time Factors
          Treatment Outcomes
          Female
      ab: Purpose: We evaluated whether 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine ([(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 ≤ 0.006, n = 6 per group). [(18)F]FDG-PET and [(18)F]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 [(18)F]FLT response.Conclusions: Therapeutic inhibition of AKT activation in acquired platinum-resistant disease can be imaged noninvasively by [(18)F]FDG-PET and [(18)F]FLT-PET warranting further assessment.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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