Using fluorodeoxythymidine to monitor anti-EGFR inhibitor therapy in squamous cell carcinoma xenografts

✍ Scribed by David M. Atkinson; Michelle J. Clarke; Ann C. Mladek; Brett L. Carlson; David P. Trump; Mark S. Jacobson; Brad J. Kemp; Val J. Lowe; Jann N. Sarkaria

• Book ID: 102847562
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 775 KB
• Volume: 30
• Category: Article
• ISSN: 1043-3074
• DOI: 10.1002/hed.20770

✦ Synopsis

Abstract

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