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Pharmacodynamic Evaluation of Irinotecan Therapy by FDG and FLT PET/CT Imaging in a Colorectal Cancer Xenograft Model

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Abstract

Purpose

Longitudinal changes of 3′-[18 F]fluoro-3′-deoxythymidine (FLT) and 2-deoxy-2-[18 F]fluoro-d-glucose (FDG) in response to irinotecan therapy in an animal model of colorectal cancer were compared.

Procedures

SCID/CB-17 mice with HCT116 tumors were treated with 50 mg/kg irinotecan by intraperitoneal injection weekly for 3 weeks. FLT and FDG-positron emission tomography (PET) were performed at baseline, the day after each treatment, and 5 days after the first treatment. Proliferation and apoptosis were evaluated by immunohistochemistry (IHC) after day 15 of imaging.

Results

Irinotecan treatment resulted in a suppression of tumor growth. Tumor FLT uptake was decreased the day after each treatment but to a lesser extent 5 days after the first treatment. FDG uptake increased the day after each treatment with a continuous increase throughout the experiment. IHC analysis of phospho-H3 and Ki67 confirmed FLT-PET results, indicating a decrease in proliferation the day after the final irinotecan treatment. Increased apoptosis monitored by caspase-3 was observed after day 15 with irinotecan treatment.

Conclusions

FLT-PET may be a better method than FDG-PET for assessing treatment response to irinotecan. Changes in imaging occur before changes in tumor volume.

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Acknowledgements

The authors thank Velitchka Bontcheva-Diaz, Jerry Clarin, Sally Schlessinger, Lauren Smithee, and Baole Wang for technical assistance and Alan Fan for critical reading of the manuscript. This work was supported by Abbott Laboratories.

Conflict of Interest

All authors are Abbott employees.

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Authors and Affiliations

  1. Translational Imaging and Biochemical Biomarkers, Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA

    Sarah R. Mudd, Kimberley D. Holich, Martin J. Voorbach, Todd B. Cole, Gerard B. Fox, Mark Day & Yanping Luo

  2. In Vivo Pharmacology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA

    David R. Reuter, Paul Tapang, Gail Bukofzer, Cherrie K. Donawho & Joann P. Palma

  3. Exploratory Statistics, Global Data Management and Statistics, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA

    Arunava Chakravartty

  4. Dept. AP4A-1, 100 Abbott Park Road, Abbott Park, IL, 60064, USA

    Sarah R. Mudd

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  1. Sarah R. Mudd
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  2. Kimberley D. Holich
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  3. Martin J. Voorbach
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Correspondence to Sarah R. Mudd.

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Mudd, S.R., Holich, K.D., Voorbach, M.J. et al. Pharmacodynamic Evaluation of Irinotecan Therapy by FDG and FLT PET/CT Imaging in a Colorectal Cancer Xenograft Model. Mol Imaging Biol 14, 617–624 (2012). https://doi.org/10.1007/s11307-011-0529-8

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  • DOI: https://doi.org/10.1007/s11307-011-0529-8

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