Knight James C, Koustoulidou Sofia, Cornelissen Bart
CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7LJ, UK.
Eur J Nucl Med Mol Imaging. 2017 Jun;44(6):1065-1078. doi: 10.1007/s00259-016-3604-1. Epub 2017 Jan 5.
DNA integrity is constantly challenged by endogenous and exogenous factors that can alter the DNA sequence, leading to mutagenesis, aberrant transcriptional activity, and cytotoxicity. Left unrepaired, damaged DNA can ultimately lead to the development of cancer. To overcome this threat, a series of complex mechanisms collectively known as the DNA damage response (DDR) are able to detect the various types of DNA damage that can occur and stimulate the appropriate repair process. Each DNA damage repair pathway leads to the recruitment, upregulation, or activation of specific proteins within the nucleus, which, in some cases, can represent attractive targets for molecular imaging. Given the well-established involvement of DDR during tumorigenesis and cancer therapy, the ability to monitor these repair processes non-invasively using nuclear imaging techniques may facilitate the earlier detection of cancer and may also assist in monitoring response to DNA damaging treatment. This review article aims to provide an overview of recent efforts to develop PET and SPECT radiotracers for imaging of DNA damage repair proteins.
DNA完整性不断受到内源性和外源性因素的挑战，这些因素可改变DNA序列，导致诱变、异常转录活性和细胞毒性。若不修复，受损的DNA最终可导致癌症的发生。为了克服这一威胁，一系列统称为DNA损伤反应（DDR）的复杂机制能够检测可能发生的各种类型的DNA损伤，并刺激适当的修复过程。每条DNA损伤修复途径都会导致细胞核内特定蛋白质的募集、上调或激活，在某些情况下，这些蛋白质可能是分子成像的有吸引力的靶点。鉴于DDR在肿瘤发生和癌症治疗过程中已明确的作用，利用核成像技术无创监测这些修复过程的能力可能有助于早期发现癌症，也有助于监测对DNA损伤治疗的反应。本文综述旨在概述近期开发用于DNA损伤修复蛋白成像的PET和SPECT放射性示踪剂的研究进展。
