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FDG-PET for Pharmacodynamic Assessment of the Fatty Acid Synthase Inhibitor C75 in an Experimental Model of Lung Cancer

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Abstract

Purpose

Fatty acid synthase (FAS) is an emerging target for anticancer therapy with a variety of new FAS inhibitors being explored in preclinical models. The aim of this study was to use positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) to monitor the effects of the FAS inhibitor C75 on tumor glucose metabolism in a rodent model of human A549 lung cancer.

Materials and Methods

After a baseline FDG-PET scan, C75 was administered and post-treatment scans were performed serially. FAS activity was measured in treated animals ex vivo by [14C]acetate incorporation in animals euthanized in parallel to those imaged.

Results

Longitudinally measured metabolic volumes of interest and tumor/background ratios demonstrated a transient, reversible decrease in glucose metabolism and tumor metabolic volume after treatment, with the peak effect seen at 4 h. FDG-PET measurements correlated with changes in tumor FAS activity measured ex vivo.

Conclusions

Because C75 causes an effect that is shorter in duration than expected, modification of the current weekly dosing regimen should be considered. These results demonstrate the utility of small animal FDG-PET in assessing the pharmacodynamics of new anticancer agents in preclinical models.

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Acknowledgments

The authors appreciate the suggestions and comments of Dr. Jurgen Seidel and Michael Green of the National Institutes of Health, Clinical Center. This work was supported by grants from the National Cancer Institute (P50 CA058184, R01 CA101232 and U24 CA92871).

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Author notes

  1. Jae Sung Lee

    Present address: Seoul National University College of Medicine, Seoul, 110-744, South Korea

Authors and Affiliations

  1. Department of Radiology, Johns Hopkins Medical Institutions, 1550 Orleans Street, 492 CRB II, Baltimore, Maryland, 21231, USA

    Jae Sung Lee, Ruth L. Hagemann & Martin G. Pomper

  2. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, 21231, USA

    Hajime Orita, Francis P. Kuhajda & Edward Gabrielson

  3. Department of Molecular and Comparative Pathobiology, Johns Hopkins Medical Institutions, Baltimore, Maryland, 21231, USA

    Kathleen Gabrielson & Sara Alvey

Authors
  1. Jae Sung Lee
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  2. Hajime Orita
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  3. Kathleen Gabrielson
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  4. Sara Alvey
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  5. Ruth L. Hagemann
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  6. Francis P. Kuhajda
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  7. Edward Gabrielson
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  8. Martin G. Pomper
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Corresponding author

Correspondence to Martin G. Pomper.

Additional information

Jae Sung Lee and Hajime Orita contributed equally to this work

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Lee, J.S., Orita, H., Gabrielson, K. et al. FDG-PET for Pharmacodynamic Assessment of the Fatty Acid Synthase Inhibitor C75 in an Experimental Model of Lung Cancer. Pharm Res 24, 1202–1207 (2007). https://doi.org/10.1007/s11095-007-9264-x

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  • DOI: https://doi.org/10.1007/s11095-007-9264-x

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