ImmunoPET Imaging of Trop2 Expression in Bladder Cancer Using [64Cu]Cu-NOTA-Trodelvy

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Wenpeng Huang, Tianyao Wang, Fangfang Chao, Qi Yang, Jason C. Mixdorf, Liming Li, Jonathan W. Engle, Yu Fan*, Lei Kang* and Weibo Cai*, 
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Abstract

Trop2 exhibits significantly elevated expression in numerous solid malignancies, playing a crucial role in tumor advancement, whereas its presence in healthy tissues is minimal. In this study, we investigated Trop2 expression in bladder cancer models using [64Cu]Cu-NOTA-Trodelvy for immunoPET imaging. In HT-1376 models, [64Cu]Cu-NOTA-Trodelvy effectively visualized tumor as early as 12 h p.i. (10.30 ± 1.45% ID/g), with tumor uptake increasing and peaking at 48 h p.i. (13.73 ± 1.16% ID/g), highlighting its potential for tumor imaging. Control groups also demonstrated low tumor uptake (5.27 ± 1.14% ID/g at 48 h in the blocking group; 6.33 ± 0.74% ID/g at 48 h in UM-UC-3; 4.50 ± 0.30% ID/g at 48 h in the [64Cu]Cu-NOTA-IgG group). Long-term fluorescence imaging further confirmed the tumor uptake rate in the IRDye 800CW-Trodelvy group was significantly higher than in the IRDye 800CW-Trodelvy blockade group (P < 0.001). Our findings demonstrated that [64Cu]Cu-NOTA-Trodelvy enables specific and prolonged tumor accumulation in bladder cancer models, providing precise and noninvasive monitoring of Trop2 expression.

Abstract Image

[64Cu]Cu-NOTA-Trodelvy在膀胱癌组织中Trop2表达的免疫pet成像
Trop2在许多实体恶性肿瘤中表现出显著的表达升高,在肿瘤进展中起着至关重要的作用,而它在健康组织中的存在是最小的。在本研究中,我们使用[64Cu]Cu-NOTA-Trodelvy进行免疫pet成像,研究了膀胱癌模型中Trop2的表达。在HT-1376模型中,[64Cu]Cu-NOTA-Trodelvy早在12 h p.i.(10.30±1.45% ID/g)就能有效地显示肿瘤,肿瘤摄取增加,并在48 h p.i.(13.73±1.16% ID/g)时达到峰值,突出了其在肿瘤成像中的潜力。对照组在48 h时也表现出较低的肿瘤摄取(5.27±1.14% ID/g);在UM-UC-3中,48 h时ID/g为6.33±0.74%;[64Cu]Cu-NOTA-IgG组48 h为4.50±0.30% ID/g)。长期荧光成像进一步证实,IRDye 800CW-Trodelvy组的肿瘤摄取率显著高于IRDye 800CW-Trodelvy阻断组(P <;0.001)。我们的研究结果表明,[64Cu]Cu-NOTA-Trodelvy能够在膀胱癌模型中特异性和长时间的肿瘤积累,提供了对Trop2表达的精确和无创监测。
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来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
期刊介绍: Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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