正电子发射断层扫描和光学成像监测曲妥珠单抗与卟啉的生物正交diols - alder Click化学。

IF 4 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-05-12 DOI:10.1021/acs.bioconjchem.5c00056

Sara R D Gamelas, Shayla Shmuel, Cristina Simó, Alex Vanover, João P C Tomé, Augusto C Tomé, Leandro M O Lourenço, Patrícia M R Pereira

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引用次数: 0

摘要

点击化学，允许荧光团卟啉(Por)-四嗪（Tz）与人表皮生长因子受体2 （HER2）靶向曲妥珠单抗与反式环烯（TCO）偶联的体内偶联。体外实验证实了Por-Tz与曲妥珠单抗- tco之间成功的点击反应，并验证了保留的曲妥珠单抗免疫反应性（HER2结合无显著变化，p < 0.05）。注射后48 h， [89Zr] zr - dfo -曲妥珠单抗- tco的正电子发射断层扫描（PET）显示每克肿瘤的注射剂量为17.1±2.9%。光学成像显示，与单独使用Por-Tz相比，Por-Tz的点击组增加了~ 10倍。该临床前数据证明了her2表达肿瘤的双重PET和光学成像的预靶向方法。

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Positron Emission Tomography and Optical Imaging to Monitor Bioorthogonal Diels-Alder Click Chemistry of Trastuzumab with a Porphyrin.

Click chemistry to allow in vivo conjugation of a fluorophore porphyrin (Por)-tetrazine (Tz) with the human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab conjugated with trans-cyclooctene (TCO) is described here. In vitro experiments confirmed successful click reactions between Por-Tz and trastuzumab-TCO and validated preserved trastuzumab immunoreactivity (no significant change in HER2 binding, p > 0.05). Positron emission tomography (PET) of [⁸⁹Zr]Zr-DFO-trastuzumab-TCO demonstrated 17.1 ± 2.9% injected dose per gram of tumor at 48 h postinjection. Optical imaging showed an ∼10-fold increase in the click group for Por-Tz when compared with Por-Tz alone. This preclinical data demonstrate a pretargeted approach for dual PET and optical imaging of HER2-expressing tumors.

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来源期刊

Bioconjugate Chemistry 生物-化学综合

CiteScore

9.00

自引率

2.10%

发文量

236

审稿时长

1.4 months

期刊介绍： Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.