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^99mTc-Interleukin-2 Scintigraphy as a Potential Tool for Evaluating Tumor-Infiltrating Lymphocytes in Melanoma Lesions: A Validation Study

¹ Nuclear Medicine Unit, Departments of Clinical Sciences and Radiological Sciences, Second Faculty of Medicine, University "La Sapienza," Rome, Italy
² Department of Biopathology and Diagnostic Imaging, University "Tor Vergata," Rome, Italy
³ Nuclear Medicine Unit, "Regina Apostolorum" Hospital, Albano Laziale, Rome, Italy
⁴ Department of Nuclear Medicine, St. Bartholomew’s Hospital, Cancer Research U.K., London, United Kingdom
⁵ Department of Dermatology and Plastic Surgery, University "La Sapienza," Rome, Italy

Cutaneous melanoma is often characterized by the presence of tumor-infiltrating lymphocytes (TILs). The degree of such infiltration and cell activation are considered significant prognostic factors reflecting the host’s immune response to the tumor; thus, patients with peritumoral infiltration may have a better prognosis and may also achieve a better response to interleukin-2 (IL2) immunotherapy. There is evidence that the expression of cluster designation (CD) 25 antigen (IL2 receptor [IL2R]) is a good marker of activity of T lymphocytes against melanoma cells. The aim of this study was to evaluate in vivo the binding of ^99mTc-IL2 to lymphocytes infiltrating cutaneous melanoma and to determine whether such uptake correlates with immunologic and histologic data, thus providing useful prognostic information for IL2 therapy in patients with advanced disease. Methods: Thirty patients with cutaneous lesions suspected of being melanoma were studied. Planar -camera images over known tumor sites were acquired 1 h after the injection of 111–185 MBq of ^99mTc-IL2. Tumor uptake of ^99mTc-IL2 was measured as a target-to-background (T/B) radioactivity ratio. All patients underwent surgery, and histologic evaluation of the resected lesion was performed. The percentage of different peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD16, CD25) and the percentage of IL2R-positive tumor cells on histologic sections were also measured. Results: At final histology, 21 lesions were found to be melanoma and 9 were classified as benign. In 15 of 21 (71%) melanomas and 2 of 9 (22%) benign cutaneous lesions, we found uptake of ^99mTc-IL2. The calculated T/B ratios correlated significantly with the number of IL2R-positive TILs. Conclusion: ^99mTc-IL2 scintigraphy provides a means of in vivo measurement of the extent of tumor infiltration of IL2R-positive cells, thereby providing valuable prognostic information for selection of patients who may benefit from IL2 immunotherapy.

Key Words: interleukin-2 • scintigraphy • melanoma • tumor-infiltrating lymphocytes

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