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Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of [18F]fluoro-2-deoxyglucose and 3'-deoxy-3'-[18F]fluorothymidine imaging.

ABSTRACT: To determine whether treatment response to the Aurora B kinase inhibitor, AZD1152, could be monitored early in the course of therapy by noninvasive [(18)F]-labeled fluoro-2-deoxyglucose, [(18)F]FDG, and/or 3'-deoxy-3'-[(18)F]fluorothymidine, [(18)F]FLT, PET imaging.AZD1152-treated and control HCT116 and SW620 xenograft-bearing animals were monitored for tumor size and by [(18)F]FDG, and [(18)F]FLT PET imaging. Additional studies assessed the endogenous and exogenous contributions of thymidine synthesis in the two cell lines.Both xenografts showed a significant volume-reduction to AZD1152. In contrast, [(18)F]FDG uptake did not demonstrate a treatment response. [(18)F]FLT uptake decreased to less than 20% of control values in AZD1152-treated HCT116 xenografts, whereas [(18)F]FLT uptake was near background levels in both treated and untreated SW620 xenografts. The EC(50) for AZD1152-HQPA was approximately 10 nmol/L in both SW620 and HCT116 cells; in contrast, SW620 cells were much more sensitive to methotrexate (MTX) and 5-Fluorouracil (5FU) than HCT116 cells. Immunoblot analysis demonstrated marginally lower expression of thymidine kinase in SW620 compared with HCT116 cells. The aforementioned results suggest that SW620 xenografts have a higher dependency on the de novo pathway of thymidine utilization than HCT116 xenografts.AZD1152 treatment showed antitumor efficacy in both colon cancer xenografts. Although [(18)F]FDG PET was inadequate in monitoring treatment response, [(18)F]FLT PET was very effective in monitoring response in HCT116 xenografts, but not in SW620 xenografts. These observations suggest that de novo thymidine synthesis could be a limitation and confounding factor for [(18)F]FLT PET imaging and quantification of tumor proliferation, and this may apply to some clinical studies as well.

SUBMITTER: Moroz MA

PROVIDER: S-EPMC3079195 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of [18F]fluoro-2-deoxyglucose and 3'-deoxy-3'-[18F]fluorothymidine imaging.

Moroz Maxim A MA Kochetkov Tatiana T Cai Shangde S Wu Jiyuan J Shamis Mikhail M Nair Jayasree J de Stanchina Elisa E Serganova Inna I Schwartz Gary K GK Banerjee Debabrata D Bertino Joseph R JR Blasberg Ronald G RG

Clinical cancer research : an official journal of the American Association for Cancer Research 20110118 5

<h4>Purpose</h4>To determine whether treatment response to the Aurora B kinase inhibitor, AZD1152, could be monitored early in the course of therapy by noninvasive [(18)F]-labeled fluoro-2-deoxyglucose, [(18)F]FDG, and/or 3'-deoxy-3'-[(18)F]fluorothymidine, [(18)F]FLT, PET imaging.<h4>Experimental design</h4>AZD1152-treated and control HCT116 and SW620 xenograft-bearing animals were monitored for tumor size and by [(18)F]FDG, and [(18)F]FLT PET imaging. Additional studies assessed the endogenous ...[more]

PMID: 21245090

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Dataset Information

Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of [18F]fluoro-2-deoxyglucose and 3'-deoxy-3'-[18F]fluorothymidine imaging.

Publications

Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of [18F]fluoro-2-deoxyglucose and 3'-deoxy-3'-[18F]fluorothymidine imaging.

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