Development of Structurally Identical Therapeutic and Diagnostic Agents for Image-Guided Boron Neutron Capture Therapy: c(RGD-BPA-K) Peptide with ¹²⁵I/^natI Albumin-Binding Moiety.

IF 4.5 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Pharmaceutics Pub Date : 2025-06-02 Epub Date: 2025-04-30 DOI:10.1021/acs.molpharmaceut.5c00291

Iqra Bibi, Kyung Jun Kang, Jung Young Kim, Sajid Mushtaq, Ji-Ae Park

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引用次数: 0

Abstract

The development of boron neutron capture therapy (BNCT) agents and structurally similar radiolabeled counterparts for diagnostic imaging is an area of significant interest. In this study, we designed structurally same compounds, c(RGD-BPA-K)(PEG₂-(4-iodophenylbutyl)) (compound 1) and its radioiodinated counterpart, c(RGD-BPA-K)(PEG₂-(4-[¹²⁵I]iodophenylbutyl)) ([¹²⁵I]1), for efficient BNCT and SPECT/CT imaging, respectively. An albumin-binding moiety was introduced into the compound to enhance the blood circulation time and tumor accumulation. We evaluated the efficacy of compound 1 and [¹²⁵I]1 in U87MG tumor-bearing mice using SPECT/CT imaging, biodistribution analysis, and inductively coupled plasma mass spectrometry. Both compound 1 and [¹²⁵I]1 displayed similar pharmacokinetics, high blood retention, and substantial accumulation in U87MG tumors. This study highlights the potential of compound 1 and [¹²⁵I]1 for SPECT/CT-guided BNCT. The structural identity between the therapeutic and diagnostic agents in BNCT can enhance its therapeutic efficacy. Further structural modifications to increase boron concentration in tumors, as well as thermal neutron irradiation studies, may be necessary to fully explore the potential of our novel BNCT agent.

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具有125I/natI白蛋白结合片段的c（RGD-BPA-K）肽在图像引导硼中子俘获治疗和诊断中的应用

发展硼中子俘获治疗（BNCT）剂和结构类似的放射性标记对应物用于诊断成像是一个重要的兴趣领域。在本研究中，我们设计了结构相同的化合物c(RGD-BPA-K)（PEG2-（4-碘苯基丁基））（化合物1）及其放射性碘化对应物c(RGD-BPA-K)（PEG2-（4-[125I]碘苯基丁基））（[125I]1），分别用于高效的BNCT和SPECT/CT成像。在化合物中引入白蛋白结合片段，以延长血液循环时间和肿瘤积累。我们通过SPECT/CT成像、生物分布分析和电感耦合等离子体质谱分析来评估化合物1和[125I]1对U87MG荷瘤小鼠的疗效。化合物1和[125I]1在U87MG肿瘤中表现出相似的药代动力学、高血潴留和大量积累。本研究强调了化合物1和[125I]1在SPECT/ ct引导下的BNCT中的潜力。BNCT中治疗剂和诊断剂的结构一致性可以提高其治疗效果。进一步的结构修饰以增加肿瘤中的硼浓度，以及热中子辐照研究，可能是充分挖掘我们的新型BNCT剂潜力的必要条件。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.