Background/Objectives: Radiolabeled interleukin-2 (IL2) could allow for imaging activated T-lymphocytes in the tumor microenvironment (TME). The aims of this study were to assess the shelf life of a lyophilized kit containing THP-desIL2 to allow for the labeling of IL2 with 68Ga at room temperature and to test the in vitro binding of 68Ga-THP-desIL2 on different T-cell populations in order to determine which specific T-cell subset expresses the CD25 subunit of the IL2 receptor (IL2R). Methods: desIL2 was conjugated with THP and lyophilized. 68Ga labeling was performed and several quality controls, including HPLC, iTLC and SDS-PAGE, were carried out at different storage times (1, 3 and 6 months) and temperatures (4 °C and −80 °C). Moreover, flow cytometric analysis on different T-cell populations and the in vitro and competitive binding of 68Ga-THP-desIL2 were performed. Results: The lyophilized kit of THP-desIL2 was stable up to 6 months at −80 °C, preserving its sterility, integrity and acceptable values of labeling yield (51.80 ± 3.74%), radiochemical purity (>96%) and specific activity (5.59 ± 0.40 MBq/µg). Binding of 68Ga-THP-desIL2 on activated lymphocytes was specific and exhibited a low dissociation constant from IL2R on stimulated Tregs (Kd: 10−9–10−10 mol/L). Conclusions: We assessed the shelf life of a lyophilized kit containing THP-desIL2 for the easy labeling of IL2 with 68Ga at room temperature. The kit can be stored at −80 °C up to 6 months, thus facilitating the adoption of 68Ga-THP-desIL2 into clinical practice. 68Ga-THP-desIL2 showed high affinity and specificity for CD25 on activated T-lymphocytes, particularly Tregs, thus opening new opportunities for imaging immune cells trafficking in the TME.
Validation of a Ready-to-Use Lyophilized Kit for Labeling IL2 with 68Ga: A New Avenue for Imaging Activated T-lymphocytes in Tumor Microenvironment / Lauri, Chiara; Bentivoglio, Valeria; Varani, Michela; Cammarata, Ilenia; Sartori, Giorgia; Piconese, Silvia; Campagna, Giuseppe; Signore, Alberto. - In: JOURNAL OF CLINICAL MEDICINE. - ISSN 2077-0383. - 14:16(2025). [10.3390/jcm14165658]
Validation of a Ready-to-Use Lyophilized Kit for Labeling IL2 with 68Ga: A New Avenue for Imaging Activated T-lymphocytes in Tumor Microenvironment
Lauri, Chiara
;Bentivoglio, Valeria;Varani, Michela;Cammarata, Ilenia;Sartori, Giorgia;Piconese, Silvia;Campagna, Giuseppe;Signore, Alberto
2025
Abstract
Background/Objectives: Radiolabeled interleukin-2 (IL2) could allow for imaging activated T-lymphocytes in the tumor microenvironment (TME). The aims of this study were to assess the shelf life of a lyophilized kit containing THP-desIL2 to allow for the labeling of IL2 with 68Ga at room temperature and to test the in vitro binding of 68Ga-THP-desIL2 on different T-cell populations in order to determine which specific T-cell subset expresses the CD25 subunit of the IL2 receptor (IL2R). Methods: desIL2 was conjugated with THP and lyophilized. 68Ga labeling was performed and several quality controls, including HPLC, iTLC and SDS-PAGE, were carried out at different storage times (1, 3 and 6 months) and temperatures (4 °C and −80 °C). Moreover, flow cytometric analysis on different T-cell populations and the in vitro and competitive binding of 68Ga-THP-desIL2 were performed. Results: The lyophilized kit of THP-desIL2 was stable up to 6 months at −80 °C, preserving its sterility, integrity and acceptable values of labeling yield (51.80 ± 3.74%), radiochemical purity (>96%) and specific activity (5.59 ± 0.40 MBq/µg). Binding of 68Ga-THP-desIL2 on activated lymphocytes was specific and exhibited a low dissociation constant from IL2R on stimulated Tregs (Kd: 10−9–10−10 mol/L). Conclusions: We assessed the shelf life of a lyophilized kit containing THP-desIL2 for the easy labeling of IL2 with 68Ga at room temperature. The kit can be stored at −80 °C up to 6 months, thus facilitating the adoption of 68Ga-THP-desIL2 into clinical practice. 68Ga-THP-desIL2 showed high affinity and specificity for CD25 on activated T-lymphocytes, particularly Tregs, thus opening new opportunities for imaging immune cells trafficking in the TME.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.


