AJNMMI Copyright © 2011-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA
Am J Nucl Med Mol Imaging 2013;3(1):16-31

Original Article
Utility of 3’-[18F]fluoro-3’-deoxythymidine as a PET
tracer to monitor response to gene therapy in a
xenograft model of head and neck carcinoma

Neale S Mason, Brian J Lopresti, James Ruszkiewicz, Xinxin Dong, Sonali Joyce, George Leef, Malabika Sen, Abdus S Wahed,
Chester A Mathis, Jennifer R Grandis, Sufi M Thomas

Departments of Radiology, Biostatistics, Otolaryngology and Pharmacology and Chemical Biology, University of
Pittsburgh and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

Received July 10, 2012; Accepted October 2, 2012; Epub January 5, 2013; Published January 15, 2013

Abstract: Noninvasive imaging methodologies are needed to assess treatment responses to novel molecular targeting
approaches for the treatment of squamous cell carcinoma of the head and neck (SCCHN). Computer tomography
and magnetic resonance imaging do not effectively distinguish tumors from fibrotic tissue commonly associated
with SCCHN tumors. Positron emission tomography (PET) offers functional non-invasive imaging of tumors. We
determined the uptake of the PET tracers 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 3’-[18F]Fluoro-3’-deoxythymidine
([18F]FLT) in several SCCHN xenograft models. In addition, we evaluated the utility of [18F]FLT microPET
imaging in monitoring treatment response to an EGFR antisense approach targeted therapy that has shown safety
and efficacy in a phase I trial. Two of the 3 SCCHN xenograft models tested demonstrated no appreciable uptake
or retention of [18F]FDG, but consistent accumulation of [18F]FLT. The third tumor xenograft SCCHN model (Cal33)
demonstrated variable uptake of both tracers. SCCHN xenografts (1483) treated with EGFR antisense gene therapy
decreased tumor volumes in 4/6 mice. Reduced uptake of [18F]FLT was observed in tumors that responded to epidermal
growth factor antisense (EGFRAS) gene therapy compared to non-responding tumors or tumors treated with
control sense plasmid DNA. These findings indicate that [18F]FLT PET imaging may be useful in monitoring SCCHN
response to molecular targeted therapies, while [18F]FDG uptake in SCCHN xenografts may not be reflective of the
level of metabolic activity characteristic of human SCCHN tumors. (ajnmmi1207001).

Keywords: Squamous cell carcinoma of the head and neck (SCCHN), positron emission tomography (PET), 2-deoxy-
2-[18F]fluoro-D-glucose ([18F]FDG), 3’-[18F]Fluoro-3’-deoxythymidine ([18F]FLT), epidermal growth factor receptor
(EGFR), volume of interest (VOI), standardize uptake values (SUV), region of interest (ROI)

Address all correspondence to:
Dr. Sufi Mary Thomas
University of Pittsburgh, 200 Lothrop Street
W947 BST, Pittsburgh, PA 15213, USA.
Tel: +1-412-3835403; Fax: +1-412-3835409
E-mail: smt30@pitt.edu