Journal article

18F-FLT PET as a surrogate marker of drug efficacy during mTOR inhibition by everolimus in a preclinical cisplatin-resistant ovarian tumor model

N Aide, K Kinross, C Cullinane, P Roselt, K Waldeck, O Neels, D Dorow, G McArthur, RJ Hicks

Journal of Nuclear Medicine | Published : 2010

Abstract

Targeting the mammalian target of rapamycin (mTOR) pathway is a potential means of overcoming cisplatin resistance in ovarian cancer patients. Because mTOR inhibition affects cell proliferation, we aimed to study whether 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) PET could be useful for monitoring early response to treatment with mTOR inhibitors in an animal model of cisplatin-resistant ovarian tumor. Methods: BALB/c nude mice bearing subcutaneous human SKOV3 ovarian cancer xenografts were treated with either the mTOR inhibitor everolimus (5 mg/kg) or vehicle, and 18F-FLT PET was performed at baseline, day 2, and day 7 of treatment. 18F-FLT uptake was evaluated by calculation of mean standard..

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Grants

Funding Acknowledgements

This work was supported by a fellowship from the Fondation de France and by a grant from the French Ligue contre le cancer, Comite du calvados. The authors thank the animal technologists and research assistants (Rachel Walker, Susan Jackson, Kerry Ardley, Jeannette Valentan, Ekaterina Bogatyreva, and Laura Kirby) from the Centre for Molecular Imaging for caring for the animals, injecting the tracer, and acquiring the SA PET images. Dr. Aide is indebted to Dr. Delphine Lerouge for her continuous support during this work.