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Using fluorodeoxythymidine to monitor anti‐EGFR inhibitor therapy in squamous cell carcinoma xenografts
Author(s) -
Atkinson David M.,
Clarke Michelle J.,
Mladek Ann C.,
Carlson Brett L.,
Trump David P.,
Jacobson Mark S.,
Kemp Brad J.,
Lowe Val J.,
Sarkaria Jann N.
Publication year - 2008
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.20770
Subject(s) - cetuximab , erlotinib , medicine , epidermal growth factor receptor , positron emission tomography , cancer research , standardized uptake value , egfr inhibitors , head and neck squamous cell carcinoma , gene knockdown , head and neck cancer , oncology , cancer , nuclear medicine , cell culture , biology , colorectal cancer , genetics
Background 3′‐18F‐fluoro‐3′‐deoxy‐fluorothymidine ( 18 F‐FLT), a nucleoside analog, could monitor effects of molecularly targeted therapeutics on tumor proliferation. Methods We tested whether 18 F‐FLT positron emission tomography (PET) uptake changes are associated with antitumor effects of erlotinib in A431 xenografts or cetuximab in SCC1 xenografts. Results Compared with pretreatment FLT PET scans, 3 days of erlotinib in A431 reduced the standardized uptake value (SUV) by 18%, whereas placebo increased SUV by 1% ( p = .005). One week of cetuximab in SCC1 reduced SUV by 62%, whereas placebo reduced SUV by 16% ( p = .005). FLT uptake suppression following anti–epidermal growth factor receptor (EGFR) treatment was associated with reduced tumor thymidine kinase‐1 (TK1) activity. In vitro TK1 knockdown studies confirmed the importance of TK1 activity on intracellular FLT accumulation suppression. Conclusions 18 F‐FLT PET imaging detects tumor responses to EGFR‐inhibitors within days of starting therapy. This technique may identify patients likely to benefit from EGFR‐inhibitors early in their treatment course. © 2008 Wiley Periodicals, Inc. Head Neck, 2008