PT  - JOURNAL ARTICLE
AU  - Troost, Esther G.C.
AU  - Bussink, Johan
AU  - Slootweg, Piet J.
AU  - Peeters, Wenny J.M.
AU  - Merkx, Matthias A.W.
AU  - van der Kogel, Albert J.
AU  - Oyen, Wim J.G.
AU  - Kaanders, Johannes H.A.M.
TI  - Histopathologic Validation of 3′-Deoxy-3′-<sup>18</sup>F-Fluorothymidine PET in Squamous Cell Carcinoma of the Oral Cavity
AID  - 10.2967/jnumed.109.071910
DP  - 2010 May 01
TA  - Journal of Nuclear Medicine
PG  - 713--719
VI  - 51
IP  - 5
4099  - http://jnm.snmjournals.org/content/51/5/713.short
4100  - http://jnm.snmjournals.org/content/51/5/713.full
SO  - J Nucl Med2010 May 01; 51
AB  - Accelerated tumor cell repopulation is an important mechanism adversely affecting therapeutic outcome in head and neck cancer. The noninvasive assessment of the proliferative state of a tumor by PET may provide a selection tool for customized treatment. 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) is a PET tracer that is phosphorylated by thymidine kinase 1 (TK-1) and, as such, reflects cellular proliferation. Before the use of 18F-FLT PET for tumor characterization is accepted and introduced into clinical studies, validation against tumor histology is mandatory. The aim of this study was to validate 18F-FLT PET in squamous cell carcinomas of the oral cavity using immunohistochemical staining for the proliferation marker iododeoxyuridine and for TK-1. Methods: Seventeen patients with primary squamous cell carcinomas of the oral cavity underwent an 18F-FLT PET/CT scan before surgery, and iododeoxyuridine was administered 20 min before tumor resection. 18F-FLT PET/CT scans were segmented, and PET/CT volumes and PET signal intensities were calculated (mean standardized uptake value [SUVmean] and maximum standardized uptake value [SUVmax]). Multiple paraffin-embedded tumor sections were immunohistochemically stained for iododeoxyuridine and TK-1. For iododeoxyuridine, labeling indices and optical densities were calculated and correlated with SUVmean and SUVmax. TK-1 staining was visually and semiquantitatively assessed. Results: All primary tumors were identified with 18F-FLT PET but with a large range in tracer uptake (mean SUVmax, 5.9; range, 2.2–15.2). Also, there was a large variability in iododeoxyuridine labeling indices (mean, 0.09; range, 0.01–0.29) and optical densities (mean, 28.2; range, 12.6–37.8). The iododeoxyuridine optical densities correlated significantly with SUVmean and SUVmax, but the labeling indices did not. In most tumors, TK-1 staining of varying intensity was present but correlated with neither iododeoxyuridine binding nor 18F-FLT uptake. Conclusion: The current study demonstrated only a weak correlation between 18F-FLT uptake and iododeoxyuridine staining intensity in oral cavity tumors. This weak correlation may be explained by differences in biomarker characteristics, resolution, and quantification methods.