Histopathologic validation of 3'-deoxy-3'-18F-fluorothymidine PET in squamous cell carcinoma of the oral cavity.

Abstract

UNLABELLED:

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'-(18)F-fluorothymidine ((18)F-FLT) is a PET tracer that is phosphorylated by thymidine kinase 1 (TK-1) and, as such, reflects cellular proliferation. Before the use of (18)F-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 (18)F-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 (18)F-FLT PET/CT scan before surgery, and iododeoxyuridine was administered 20 min before tumor resection. (18)F-FLT PET/CT scans were segmented, and PET/CT volumes and PET signal intensities were calculated (mean standardized uptake value [SUV(mean)] and maximum standardized uptake value [SUV(max)]). 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 SUV(mean) and SUV(max). TK-1 staining was visually and semiquantitatively assessed.

RESULTS:

All primary tumors were identified with (18)F-FLT PET but with a large range in tracer uptake (mean SUV(max), 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 SUV(mean) and SUV(max), but the labeling indices did not. In most tumors, TK-1 staining of varying intensity was present but correlated with neither iododeoxyuridine binding nor (18)F-FLT uptake.

CONCLUSION:

The current study demonstrated only a weak correlation between (18)F-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.

• Authors: Esther G C Troost, Johan Bussink, Piet J Slootweg, Wenny J M Peeters, Matthias A W Merkx, Albert J van der Kogel, Wim J G Oyen, Johannes H A M Kaanders
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 51 Issue 5 Pg. 713-9 (May 2010) ISSN: 1535-5667 [Electronic] United States
• PMID: 20395329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Dideoxynucleosides
• Ki-67 Antigen
• Radiopharmaceuticals
• Thymidine Kinase
• thymidine kinase 1
• Idoxuridine
• alovudine

Topics

• Biomarkers
• Carcinoma, Squamous Cell (diagnostic imaging, pathology)
• Dideoxynucleosides
• Female
• Humans
• Idoxuridine
• Image Processing, Computer-Assisted
• Immunohistochemistry
• Ki-67 Antigen (metabolism)
• Male
• Middle Aged
• Mouth Neoplasms (diagnostic imaging, pathology)
• Phosphorylation
• Positron-Emission Tomography
• Radiopharmaceuticals
• Reproducibility of Results
• Thymidine Kinase (metabolism)
• Tomography, Emission-Computed