99mTc-interleukin-2 scintigraphy as a potential tool for evaluating tumor-infiltrating lymphocytes in melanoma lesions: a validation study.
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 gamma-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.


CONCLUSIONS
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.
Signore
Alberto
A
Nuclear Medicine Unit, Departments of Clinical Sciences and Radiological Sciences, Second Faculty of Medicine, University La Sapienza, Rome, Italy. alberto.signore@uniroma1.it
Annovazzi
Alessio
A
Barone
Raffaella
R
Bonanno
Elena
E
D'Alessandria
Calogero
C
Chianelli
Marco
M
Mather
Stephen J
SJ
Bottoni
Ugo
U
Panetta
Chiara
C
Innocenzi
Daniele
D
Scopinaro
Francesco
F
Calvieri
Stefano
S
D005240:Feasibility Studies; D006801:Humans; D007376:Interleukin-2 / Q000493:pharmacokinetics; D008214:Lymphocytes; D016246:Lymphocytes, Tumor-Infiltrating / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011379:Prognosis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology
D007376:Interleukin-2; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C481016:technetium Tc 99m interleukin 2