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¹⁸F-FLT PET Does Not Discriminate Between Reactive and Metastatic Lymph Nodes in Primary Head and Neck Cancer Patients

¹ Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; ² Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; ³ Department of Oral and Maxillofacial Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; ⁴ Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; and ⁵ Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Correspondence: For correspondence or reprints contact: Esther G.C. Troost, MD, Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: e.troost{at}rther.umcn.nl

Repopulation of clonogenic tumor cells is inversely correlated with radiation treatment outcome in head and neck squamous cell carcinomas. A functional imaging tool to assess the proliferative activity of tumors could improve patient selection for treatment modifications and could be used for evaluation of early treatment response. The PET tracer 3'-deoxy-3'-¹⁸F-fluorothymidine (¹⁸F-FLT) can image tumor cell proliferation before and during radiotherapy, and it may provide biologic tumor information useful in radiotherapy planning. In the present study, the value of ¹⁸F-FLT PET in determining the lymph node status in squamous cell carcinoma of the head and neck was assessed, with pathology as the gold standard. Methods: Ten patients with newly diagnosed stage II–IV squamous cell carcinoma of the head and neck underwent ¹⁸F-FLT PET before surgical tumor resection with lymph node dissection. Emission ¹⁸F-FLT PET and CT images of the head and neck were recorded and fused, and standardized uptake values (SUVs) were calculated. From all 18 ¹⁸F-FLT PET-positive lymph node levels and from 8 ¹⁸F-FLT PET-negative controls, paraffin-embedded lymph node sections were stained and analyzed for the endogenous proliferation marker Ki-67 and for the preoperatively administered proliferation marker iododeoxyuridine. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for ¹⁸F-FLT PET. Results: Primary tumor sites were oral cavity (n = 7), larynx (n = 2), and maxillary sinus (n = 1). Nine of the 10 patients examined had ¹⁸F-FLT PET-positive lymph nodes (SUV_mean: median, 1.2; range, 0.8–2.9), but only 3 of these patients had histologically proven metastases. All metastatic lymph nodes showed Ki-67 and iododeoxyuridine staining in tumor cells. In the remaining 7 patients, there was abundant Ki-67 and iododeoxyuridine staining of B-lymphocytes in germinal centers in PET-positive lymph nodes, explaining the high rate of false-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value of ¹⁸F-FLT PET were 100%, 16.7%, 37.5%, and 100%, respectively. Conclusion: In head and neck cancer patients, ¹⁸F-FLT PET showed uptake in metastatic as well as in nonmetastatic reactive lymph nodes, the latter due to reactive B-lymphocyte proliferation. Because of the low specificity, ¹⁸F-FLT PET is not suitable for assessment of pretreatment lymph node status. This observation may also negatively influence the utility of ¹⁸F-FLT PET for early treatment response evaluation of small metastatic nodes.

Key Words: ¹⁸F-FLT • PET/CT • staging • head and neck cancer

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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