[68Ga]Ga-interleukin-2 for imaging activated T-lymphocytes: biochemical characterization and phase I study in normal subjects.
Purpose: This study aimed to develop a ready-to-use kit for 68Ga-labelling of interleukin-2 (IL2) facilitating PET imaging of activated T-lymphocytes. Methods: Human recombinant IL2 (hrIL2) and Aldesleukin (desIL2), conjugated with two different chelators (NODAGA and THP) were compared. Conjugated-I...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 53; no. 1; pp. 544 - 557 |
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| Autores principales: | , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Dec2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=189634270&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 189634270 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Dec2025 vid: 53 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 189634270 186307250 10.1007/s00259-025-07430-9 189634270 ppf: 544 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: [68Ga]Ga-interleukin-2 for imaging activated T-lymphocytes: biochemical characterization and phase I study in normal subjects. aug: au: Signore, Alberto Galli, Filippo Varani, Michela Campagna, Giuseppe Bentivoglio, Valeria Accardo, Antonella Morelli, Giancarlo Lauri, Chiara affil: https://ror.org/02be6w209 Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, "Sapienza" University, Rome, Italy sug: ab: Purpose: This study aimed to develop a ready-to-use kit for 68Ga-labelling of interleukin-2 (IL2) facilitating PET imaging of activated T-lymphocytes. Methods: Human recombinant IL2 (hrIL2) and Aldesleukin (desIL2), conjugated with two different chelators (NODAGA and THP) were compared. Conjugated-IL2 was stored, freeze-dried at -80 °C and radiolabelled at room temperature. In vitro quality controls (iTLC, HPLC, SDS-PAGE, spectrometry and binding assays on activated T-lymphocytes) and in vivo biodistribution studies in BALB/c mice, were performed. The shelf life of the lyophilized kits was assessed up to 6 months of storage, by iTLC, HPLC and SDS-PAGE. First-in-human study was conducted in 5 volunteers by performing [68Ga]Ga-THP-desIL2 PET/CT acquisitions at several time-points, to assess biodistribution and dosimetry. Results: Mass spectrometry showed that only one molecule of THP or NODAGA is bound to N-terminus of both IL2 proteins. The most efficient conjugation was observed for THP-desIL2. [68Ga]Ga-THP-desIL2 showed higher labelling yield (LY) (59.13 ± 2.58%), radiochemical purity (RCP) (97.91 ± 0.45%) and binding affinity to its receptor on activated T-cells (Kd = 0.584 nM/L) and a more favorable biodistribution in pre-clinical studies, with rapid kidney metabolism and lower liver uptake than [68Ga]Ga-NODAGA-desIL2 and [68Ga]Ga-THP-hrIL2. Lyophilized kit of THP-desIL2 remained stable at -80 °C up to 6 months maintaining high RCP and LY. Phase I study showed a rapid plasma clearance, renal metabolism, safety and favorable dosimetry. Conclusions: We developed an efficient lyophilized kit of THP-desIL2 for 68Ga-labelling at room temperature in GMP conditions, obtaining excellent in vitro and in vivo results. [68Ga]Ga-THP-desIL2 PET/CT studies in humans showed favorable dosimetry and safety, thus highlighting its potential for a wide range of clinical applications, particularly in immune-mediated diseases and cancer. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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