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.
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All authors are Abbott employees.
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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