Abstract
Background. 3′-18F-fluoro-3′-deoxy-fluorothymidine ( 18F-FLT), a nucleoside analog, could monitor effects of molecularly targeted therapeutics on tumor proliferation. Methods. We tested whether 18F-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. 18F-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.
Original language | English (US) |
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Pages (from-to) | 790-799 |
Number of pages | 10 |
Journal | Head and Neck |
Volume | 30 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2008 |
Keywords
- Anti-EGFR inhibitor therapy
- Cetuximab
- Erlotinib
- Fluorodeoxythymidine (FLT)
- Squamous cell carcinoma xenografts
ASJC Scopus subject areas
- Otorhinolaryngology