Preclinical evaluation of DOTAGA.Glu.(FAPI)2 and DO3A.Glu.(FAPI)2 as theranostics with human dosimetry extrapolation to lutetium-177 and terbium-161 analogs.
Purpose: This study aims to assess DOTAGA.Glu.(FAPI)2 and DO3A.Glu.(FAPI)2, specifically engineered as precursors for the development of theranostic FAPI-targeted radioligands. Methods: DOTAGA.Glu.(FAPI)2 and DO3A.Glu.(FAPI)2 were radiolabeled with gallium-68 and lutetium-177, followed by in vitro (...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 53; no. 3; pp. 1887 - 1902 |
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| Autores principales: | , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Feb2026
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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=191291354&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 191291354 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: Feb2026 vid: 53 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 191291354 188704295 10.1007/s00259-025-07565-9 191291354 ppf: 1887 ppct: 15 formats: tig: atl: Preclinical evaluation of DOTAGA.Glu.(FAPI)2 and DO3A.Glu.(FAPI)2 as theranostics with human dosimetry extrapolation to lutetium-177 and terbium-161 analogs. aug: au: Bilinska, Adrianna Kumar, Naveen Gnesin, Silvano Läppchen, Tilman Menéndez, Elena Martin, Marcel Rösch, Frank Rominger, Axel Gourni, Eleni affil: https://ror.org/01q9sj412 Department of Nuclear Medicine, Inselspital, Bern University Hospital, Bern, Switzerland sug: ab: Purpose: This study aims to assess DOTAGA.Glu.(FAPI)2 and DO3A.Glu.(FAPI)2, specifically engineered as precursors for the development of theranostic FAPI-targeted radioligands. Methods: DOTAGA.Glu.(FAPI)2 and DO3A.Glu.(FAPI)2 were radiolabeled with gallium-68 and lutetium-177, followed by in vitro (lipophilicity, protein binding, saturation, internalization and externalization) studies on FAP+ CAFs. In vivo (biodistribution, metabolic stability, blood kinetics, PET/SPECT/CT imaging) and ex vivo, (autoradiography, immunohistochemistry) conducted on PC3-mice. Murine dosimetry data were extrapolated to human estimates. Results: All radioligands achievied > 98% radiochemical purity, demonstrating high FAP affinity (Kd:0.7–0.9 nM) and rapid internalization in CAFs, with differences in lipophilicity and serum protein binding. In vivo studies, for [68Ga]Ga-DOTAGA.Glu.(FAPI)2 and [68Ga]Ga-DO3A.Glu.(FAPI)2 showed high and sustained tumor uptake up to 3 h p.i. (18–19%I.A./g). For [177Lu]Lu-DOTAGA.Glu.(FAPI)2 and [177Lu]Lu-DO3A.Glu.(FAPI)2 tumor uptake was 16.2 ± 2.5 and 15 ± 1.2% IA/g at 4 h p.i., reaching 5.1 ± 0.1 and 2.8 ± 0.4%IA/g at 48 h, respectively. All radioligands exhibited low blood retention levels. PET/SPECT/CT imaging confirmed high tumor-to-background ratios. Uptake patterns correlate well with autoradiography images of heterogeneous FAP distribution in PC3-mice, while the detection of both murine and human FAP in PC3-tumors was demonstrated through immunohistochemistry. The extrapolated human absorbed dose estimates (Gy/GBq) for [177Lu]Lu-DOTAGA.Glu.(FAPI)2 were generally higher across most organs compared to [177Lu]Lu-DO3A.Glu.(FAPI)2. Human extrapolation of the 161Tb-labeled radioligands delivered on average ~ 38% higher absorbed doses in tissues as compared to their 177Lu-labeled counterparts. Conclusion: These results support the potential clinical translation of DOTAGA.Glu.(FAPI)2 and DO3A.Glu.(FAPI)2, as promising candidates for precise diagnosis and treatment of FAP-expressing malignancies. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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