Chelator Optimization and Therapeutic Potential of 188Re-FAPI for FAP-Targeted Radionuclide Therapy

IF 4 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2025-09-03 DOI:10.1021/acsmedchemlett.5c00486

Steven H. Liang*,

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Abstract

Fibroblast activation protein (FAP) has emerged as a highly promising molecular target for cancer theranostics, with current research prioritizing the optimization of FAP-targeted radiopharmaceutical pharmacokinetics. The development of diverse FAP inhibitor (FAPI) probes conjugated with therapeutic radionuclides has significantly advanced the field of FAP-targeted radionuclide therapy (FAP-TRT). Among available radionuclides, rhenium-188 has emerged as a particularly valuable theranostic radionuclide, offering the rare combination of economical availability, therapeutic β^– emissions (E_max = 2.12 MeV), and γ emissions suitable for SPECT imaging (155 keV, 15% abundance). The strategic development of ¹⁸⁸Re-labeled FAPI compounds represents a promising approach to enhance the efficacy and clinical translation of FAP-targeted radionuclide therapy. A recent study has developed and evaluated four novel ¹⁸⁸Re-labeled FAP inhibitors through rational structure optimization, which provided a cost-effective viable alternative to established therapeutic radionuclides in clinical oncology.

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188Re-FAPI螯合剂优化及其在fap靶向放射性核素治疗中的应用潜力

成纤维细胞活化蛋白（FAP）已成为一种非常有前途的癌症治疗分子靶点，目前的研究重点是优化FAP靶向的放射性药物动力学。多种FAP抑制剂（FAPI）探针与治疗性核素结合的发展，极大地推动了FAP靶向放射性核素治疗（FAP- trt）领域的发展。在可用的放射性核素中，铼-188已成为一种特别有价值的治疗性放射性核素，提供罕见的经济可用性、治疗性β -发射（Emax = 2.12 MeV）和适合SPECT成像的γ发射（155 keV， 15%丰度）。188 - re标记的FAPI化合物的战略性开发代表了一种有希望的方法来提高fap靶向放射性核素治疗的疗效和临床翻译。最近的一项研究通过合理的结构优化开发和评估了四种新的188 - re标记FAP抑制剂，为临床肿瘤学中已建立的治疗性放射性核素提供了一种具有成本效益的可行替代方案。

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

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.