Rapid and specific immunoPET imaging of Nectin-4 in gastric cancer and non-small cell lung cancer using [64Cu]Cu-NOTA-EV-F(ab')2.
Purpose: This study aimed to develop and evaluate [64Cu]Cu-NOTA-EV-F(ab')2 as a rapid and specific immunoPET imaging probe targeting Nectin-4 in gastric cancer (GC) and non-small cell lung cancer (NSCLC). Materials and methods: F(ab')2 fragments were generated from enfortumab vedotin (EV) using IdeS...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 53; no. 1; pp. 619 - 633 |
|---|---|
| Autores principales: | , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Dec2025
|
| 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=189634247&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 189634247 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: 189634247 186044717 10.1007/s00259-025-07402-z 189634247 ppf: 619 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Rapid and specific immunoPET imaging of Nectin-4 in gastric cancer and non-small cell lung cancer using [64Cu]Cu-NOTA-EV-F(ab')2. aug: au: Huang, Wenpeng Sun, Xinyao Li, Xiaoyan Hsu, Jessica C. Qiu, Yongkang DeLuca, Molly C. Engle, Jonathan W. Li, Liming Lu, Jun Wang, Tianyao Kang, Lei Cai, Weibo affil: https://ror.org/02z1vqm45 Department of Nuclear Medicine, Peking University First Hospital, 100034, Beijing, China sug: ab: Purpose: This study aimed to develop and evaluate [64Cu]Cu-NOTA-EV-F(ab')2 as a rapid and specific immunoPET imaging probe targeting Nectin-4 in gastric cancer (GC) and non-small cell lung cancer (NSCLC). Materials and methods: F(ab')2 fragments were generated from enfortumab vedotin (EV) using IdeS protease and conjugated with p-SCN-Bn-NOTA for radiolabeling with 64CuCl2. The radiochemical yield was 85.40 ± 2.43% (n = 5). In vitro binding affinity and specificity were assessed via flow cytometry and cell uptake assays using Nectin-4-positive (NCI-N87, H1975) and Nectin-4-low (HGC-27, H520) cell lines. In vivo PET imaging and biodistribution studies were conducted in murine models of GC and NSCLC to evaluate tumor targeting efficiency and tracer pharmacokinetics. Results: [64Cu]Cu-NOTA-EV-F(ab')2 demonstrated rapid tumor accumulation, with peak uptake observed at 4 h post-injection (10.23 ± 0.70%ID/g in NCI-N87 tumors, 3.03 ± 0.35%ID/g in HGC-27, 11.56 ± 1.12%ID/g in H1975, 2.77 ± 0.47%ID/g in H520). Compared to full-length EV, the tracer exhibited faster blood clearance and reduced off-target uptake. Blocking with excess EV-F(ab')2 significantly reduced subsequent tumor uptake (6.27 ± 0.49%ID/g in NCI-N87, P = 0.0029; 5.23 ± 0.31%ID/g in H1975, P = 0.00074), confirming Nectin-4 specificity. Ex vivo biodistribution analysis supported high tumor retention consistent with in vivo imaging findings. Conclusions: [64Cu]Cu-NOTA-EV-F(ab')2 offers rapid, specific, and high-contrast immunoPET imaging of Nectin-4-expressing tumors in GC and NSCLC models, highlighting its potential as a non-invasive diagnostic tool for Nectin-4-targeted cancer imaging. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|