Pharmacodynamic evaluation of irinotecan therapy by FDG and FLT PET/CT imaging in a colorectal cancer xenograft model.

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.

• Authors: Sarah R Mudd, Kimberley D Holich, Martin J Voorbach, Todd B Cole, David R Reuter, Paul Tapang, Gail Bukofzer, Arunava Chakravartty, Cherrie K Donawho, Joann P Palma, Gerard B Fox, Mark Day, Yanping Luo
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 14 Issue 5 Pg. 617-24 (Oct 2012) ISSN: 1860-2002 [Electronic] United States
• PMID: 22167582 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dideoxynucleosides
• Fluorodeoxyglucose F18
• Irinotecan
• alovudine
• Camptothecin

Topics

• Animals
• Camptothecin (analogs & derivatives, pharmacology, therapeutic use)
• Cell Line, Tumor
• Colorectal Neoplasms (diagnostic imaging, drug therapy, pathology)
• Dideoxynucleosides (pharmacokinetics)
• Female
• Fluorodeoxyglucose F18 (pharmacokinetics)
• Humans
• Immunohistochemistry
• Irinotecan
• Mice
• Mice, SCID
• Multimodal Imaging
• Positron-Emission Tomography
• Tomography, X-Ray Computed
• Tumor Burden
• Xenograft Model Antitumor Assays