Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 51, Issue 5, Pages 713-719Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.109.071910
Keywords
F-18-fluorothymidine PET; proliferation; head and neck cancer; immunohistochemistry; iododeoxyuridine; thymidine kinase
Funding
- EC [LSHC-CT-2004-505785]
- Radboud University Nijmegen Medical Centre, The Netherlands [2006-38]
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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'-F-18-fluorothymidine (F-18-FLT) is a PET tracer that is phosphorylated by thymidine kinase 1 (TK-1) and, as such, reflects cellular proliferation. Before the use of F-18-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 F-18-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 F-18-FLT PET/CT scan before surgery, and iododeoxyuridine was administered 20 min before tumor resection. F-18-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 F-18-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 F-18-FLT uptake. Conclusion: The current study demonstrated only a weak correlation between F-18-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.
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