通过加入白蛋白结合基团提高odap -尿素基放射配体的半衰期。

IF 2.5 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2025-08-07 DOI:10.1007/s11307-025-02035-y

Xiang-Yi Chen, Yan Zhang, Xiaojiang Duan, Jingming Zhang, Zhuochen Zhang, Xing Yang, Zhi-Xiao Wei, Zuo-Xiang He

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引用次数: 0

摘要

目的：前列腺特异性膜抗原靶向放射配体治疗（PSMA-RLT）是治疗转移性去势抵抗性前列腺癌（mCRPC）的一种很有前景的方法。随着以草酸二氨基丙酸尿素（ODAP-Urea）为基础的靶向PSMA的放射性配体的出现，PSMA- rlt的新范式得到了人们的关注。本研究旨在评估为PSMA-RLT制备的潜在的新型基于odap -尿素的放射性配体。方法：选择白蛋白结合部分（ABMs）进行优化。候选药物在体外进行评估，随后通过22Rv1荷瘤小鼠的生物分布和成像研究进行研究。结果：合成了5个具有特异性ABM的新型odap -尿素衍生物（CXY-18、CXY-19、CXY-20、CXY-21、CXY-23）。所有化合物对PSMA具有较高的亲和力（Ki值为0.21 ~ 3.6 nM）和较强的人白蛋白结合能力（83.4±1.6% ~ 94.6±0.4%）。[68Ga]Ga-CXY-18 (CXY-18) PET/CT表现出最高的肿瘤摄取和血液潴留特性。在22Rv1细胞系中，[68Ga]Ga-CXY-18的内化率（23.81±1.67%）高于[68Ga]Ga-PSMA-617的内化率（9.99±0.98%）。生物分布研究证实，[177Lu]Lu-CXY-18延长了血液潴留，增强了肿瘤摄取，在注射后48 h达到峰值(4 h: 27.22±3.61%ID/g；24 h: 30.61±4.96%ID/g；48 h: 33.92±2.98%ID/g；96 h: 30.97±1.87%ID/g；192 h: 9.03±3.49%ID/g)。结论：我们的研究表明，CXY-18具有较高的PSMA特异性和肿瘤摄取性，强调了其使用4-IBA治疗PSMA- rlt的潜力。

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Enhancing the Half-Life of ODAP-Urea Based Radioligands by Incorporating Albumin-Binding Moieties.

Purpose: Prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT) is a promising approach to treating metastatic castration-resistant prostate cancer (mCRPC). With the emergence of oxalyldiaminopropionic acid urea (ODAP-Urea) based radioligands targeting PSMA, novel paradigms focused on PSMA-RLT are garnering attention. This study aims to assess potentially novel ODAP-Urea-based radioligands prepared for PSMA-RLT.

Methods: Albumin binding moieties (ABMs) were selected for optimization. Candidates were evaluated in vitro and subsequently investigated through biodistribution and imaging studies in 22Rv1 tumor-bearing mice.

Results: We synthesized five novel ODAP-Urea-based derivatives (CXY-18, CXY-19, CXY-20, CXY-21, CXY-23) with specific ABM. All compounds demonstrated high affinities for PSMA (K_i values ranging from 0.21 nM to 3.6 nM) and strong human albumin protein binding abilities (83.4 ± 1.6% to 94.6 ± 0.4%). [⁶⁸Ga]Ga-CXY-18 (CXY-18) PET/CT exhibited the highest tumor uptake and blood retention properties. Moreover, the internalization of [⁶⁸Ga]Ga-CXY-18 in the 22Rv1 cell line (23.81 ± 1.67%) exceeded that of [⁶⁸Ga]Ga-PSMA-617 (9.99 ± 0.98%). Biodistribution studies confirmed prolonged blood retention and enhanced tumor uptake with [¹⁷⁷Lu]Lu-CXY-18, peaking at 48 h post-injection (4 h: 27.22 ± 3.61%ID/g; 24 h: 30.61 ± 4.96%ID/g; 48 h: 33.92 ± 2.98%ID/g; 96 h: 30.97 ± 1.87%ID/g; 192 h: 9.03 ± 3.49%ID/g).

Conclusion: Our study indicates that CXY-18 possesses high PSMA specificity and tumor uptake, underscoring its promising potential for PSMA-RLT using 4-IBA.

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.