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癌症中PARP的分子成像:最新进展

Molecular imaging of PARP in cancer: state-of-the-art.

作者信息

Filippi Luca, Urso Luca, Frantellizzi Viviana, Marzo Katia, Marzola Maria Cristina, Schillaci Orazio, Evangelista Laura

机构信息

Nuclear Medicine Unit, Department of Oncohaematology, Fondazione PTV Policlinico Tor Vergata University Hospital, Rome, Italy.

Department of Nuclear Medicine PET/CT Centre, S. Maria della Misericordia Hospital, Rovigo, Italy.

出版信息

Expert Rev Mol Diagn. 2023 Jul-Dec;23(12):1167-1174. doi: 10.1080/14737159.2023.2287503. Epub 2023 Dec 15.

DOI:10.1080/14737159.2023.2287503
PMID:38009232
Abstract

INTRODUCTION

Poly-ADP-ribose-polymerase inhibitors (PARPi), which exploit the processes of so-called 'synthetic lethality,' have been successfully implemented in oncological practice. However, not all patients respond to PARPi, and there is an unmet need for noninvasive biomarkers suitable for patient selection and monitoring during PARPi therapy.

AREAS COVERED

The first clinical applications of molecular imaging with positron emission tomography/computed tomography (PET/CT) with [18F]-FluorThanatrace ([18F]-FTT) and [18F]-PARPi, highly effective PARP-ligands, in patients with several malignancies (head and neck, ovarian, prostate, and breast cancer) are covered, with a particular focus on its potential for pre-treatment selection and follow-up.

EXPERT OPINION

By a search made on the most common database, such as PubMed and Google Scholar in a period from January 2010 and 2023, first clinical evidence suggests that PET/CT with [18F]-FTT and [18F]-PARPi might represent a reliable tool for in vivo imaging and quantification of PARP-1 expression in ovarian, prostate, breast, head, and neck cancer, supporting their potential usefulness for patient selection before PARPi-therapies. In addition, a reduction in [18F]-FTT uptake has been registered after therapy initiation and seems to be correlated with patient outcome after PARPi-based regimens. Further studies are needed to better address the value of PARPI-radiolabeled PET imaging in these clinical settings, especially as it concerns technical features such as optimal scan modality (dynamic vs. static) and timing.

摘要

引言

聚-ADP-核糖聚合酶抑制剂(PARPi)利用所谓的“合成致死”过程,已在肿瘤学实践中成功应用。然而,并非所有患者都对PARPi有反应,对于适用于PARPi治疗期间患者选择和监测的非侵入性生物标志物仍有未满足的需求。

涵盖领域

本文涵盖了使用[18F]-氟噻那曲([18F]-FTT)和[18F]-PARPi(高效PARP配体)进行正电子发射断层扫描/计算机断层扫描(PET/CT)分子成像在多种恶性肿瘤(头颈癌、卵巢癌、前列腺癌和乳腺癌)患者中的首次临床应用,特别关注其在治疗前选择和随访方面的潜力。

专家观点

通过在2010年1月至2023年期间在最常见的数据库(如PubMed和谷歌学术)中进行检索,初步临床证据表明,使用[18F]-FTT和[18F]-PARPi的PET/CT可能是一种可靠的工具,用于在体内成像和定量卵巢癌、前列腺癌、乳腺癌、头颈癌中的PARP-1表达,支持它们在PARPi治疗前用于患者选择的潜在用途。此外,在开始治疗后已记录到[18F]-FTT摄取减少,并且似乎与基于PARPi的治疗方案后的患者预后相关。需要进一步研究以更好地阐明PARPI放射性标记PET成像在这些临床环境中的价值,特别是涉及诸如最佳扫描方式(动态与静态)和时间等技术特征方面。

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引用本文的文献

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Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging.探索PARP抑制剂的放射化学:治疗与成像的新时代。
EJNMMI Radiopharm Chem. 2025 Jul 3;10(1):37. doi: 10.1186/s41181-025-00364-5.
2
PARP-Targeted Radiotheranostics with Auger Electrons: An Updated Overview.基于俄歇电子的PARP靶向放射诊疗学:最新综述
Curr Issues Mol Biol. 2024 Mar 31;46(4):3039-3049. doi: 10.3390/cimb46040190.