ImmunoPET imaging of Trop2 expression in triple-negative breast cancer using [64Cu]Cu-NOTA-Trodelvy-F(ab')2.
Purpose: The Trop2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan (Trodelvy) has demonstrated remarkable efficacy in patients with metastatic triple-negative breast cancer (TNBC). ImmunoPET imaging offers a noninvasive method to visualize the expression and distribution of target anti...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 52; no. 9; pp. 3223 - 3238 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jul2025
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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=186337123&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 186337123 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: Jul2025 vid: 52 iid: 9 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 186337123 183229681 10.1007/s00259-025-07167-5 186337123 ppf: 3223 ppct: 15 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: ImmunoPET imaging of Trop2 expression in triple-negative breast cancer using [64Cu]Cu-NOTA-Trodelvy-F(ab')2. aug: au: Huang, Wenpeng Zhang, Yuwei Xiao, Xiaoyan Yang, Qi Mixdorf, Jason C. Sun, Xinyao Engle, Jonathan W. Fan, Yu Li, Liming Kang, Lei Cai, Weibo affil: https://ror.org/02z1vqm45 Department of Nuclear Medicine, Peking University First Hospital, No. 8 Xishiku Str., Xicheng Dist., 100034, Beijing, China sug: ab: Purpose: The Trop2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan (Trodelvy) has demonstrated remarkable efficacy in patients with metastatic triple-negative breast cancer (TNBC). ImmunoPET imaging offers a noninvasive method to visualize the expression and distribution of target antigens in vivo. In this study, we developed F(ab')2 fragments of Trodelvy for immunoPET imaging to detect Trop2 expression in TNBC models, aiming to achieve a shorter imaging window. Materials and methods: Trodelvy-F(ab')2 was prepared using the IdeS protease kit and purified with Magne Protein A beads and MagneHis™ Ni Particles. The products were characterized by non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-performance liquid chromatography. Trodelvy-F(ab')2 was subsequently conjugated with p-SCN-Bn-NOTA (NOTA) for radiolabeling with 64Cu. ImmunoPET imaging using [64Cu]Cu-NOTA-Trodelvy-F(ab')2 was conducted at multiple time points to assess its in vivo targeting capability. Immunohistochemical and immunofluorescence analyses were performed on tumor tissues obtained from tumor-bearing mice. Results: The radiochemical yield of [64Cu]Cu-NOTA-Trodelvy-F(ab')2 exceeded 90%, with a radiochemical purity greater than 99%. High Trop2 expression was observed in MDA-MB-468 cells, whereas MDST8 cells exhibited low expression. The apparent dissociation constant (KD) of [64Cu]Cu-NOTA-Trodelvy-F(ab')2 for MDA-MB-468 cells was determined to be 14.60 nM. ImmunoPET imaging revealed clear uptake of [64Cu]Cu-NOTA-Trodelvy-F(ab')2 in MDA-MB-468 tumors as early as 4 h post-injection (p.i.) (8.20 ± 0.98%ID/g), peaking at 12 h p.i. (11.13 ± 0.45%ID/g). Uptake was significantly higher compared to the MDST8 group (3.37 ± 0.45%ID/g at 4 h; 5.77 ± 0.74%ID/g at 12 h) and the blocking group (2.67 ± 0.21%ID/g at 4 h; 3.07 ± 0.37%ID/g at 12 h). [64Cu]Cu-NOTA-Trodelvy-F(ab')2 achieved significantly higher tumor-to-heart ratios in MDA-MB-468 tumors (3.87 ± 0.58 vs. 0.74 ± 0.19, P = 0.0019) at 12 h p.i., compared to [64Cu]Cu-NOTA-Trodelvy, indicating superior tumor contrast. Conclusions: Our findings indicate that [64Cu]Cu-NOTA-Trodelvy-F(ab')2 exhibits rapid, specific, and sustained tumor accumulation in TNBC models, enabling precise and noninvasive monitoring of Trop2 expression. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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