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Information obtained on the IL-2 receptor status of tumour infiltrating lymphocytes in patients suffering from squamous cell carcinoma of the head and neck (SSCHN) before and after IL-2 treatment may lead to a better understanding of the immunological changes and related kinetics induced at the tumour level and ultimately to a strategy that allows selection of those patients that will benefit from IL-2 therapy. This study set out to assess the relationship between 123I-IL2 single-photon emission computed tomography (SPECT) findings and the presence of IL-2 receptors (CD25 staining) on tumour-infiltrating lymphocytes as well as on SCCHN tumour cells in patients suffering from SCCHN.Seventeen consecutive patients (12 men; mean age, 57 years) highly suspected to suffer from SSCHN were prospectively included in the study. All patients underwent planar and whole body 123I-IL2 scintigraphy and underwent surgery or had a biopsy taken within 1 week from imaging. Surgical resected primary lesions as well as biopsy material from primary tumours were histologically analysed with respect to the presence and intensity of CD25 expression on tumour infiltrating lymphocytes and tumour cells (HSCORE). Tumor-to-background (T/N) ratios of the primary tumour derived from planar and tomographic 123I-IL2 scintigraphy were related to the results derived from histology.All patients suffered from SSCHN. T/N ratios derived from SPECT images were significantly correlated with CD25 lymphocyte HSCOREs (r = 0.66; p = 0.03), but not with CD25 tumour cell HSCOREs.123I-IL-2 SPECT imaging allows for non-invasive imaging of the relative amount of IL-2 receptors present on tumour infiltrating lymphocytes in SCCHN.