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. 2016 Jan 28;6(1):94-101.
eCollection 2016.

[(18)F]FluorThanatrace uptake as a marker of PARP1 expression and activity in breast cancer (VSports最新版本)

Christine E Edmonds  1 , Mehran Makvandi  1 , Brian P Lieberman  1 , Kuiying Xu  1 , Chenbo Zeng  1 , Shihong Li  1 , Catherine Hou  1 , Hsiaoju Lee  1 , Roger A Greenberg  2 , David A Mankoff  1 , Robert H Mach  1
Affiliations

[(18)F]FluorThanatrace uptake as a marker of PARP1 expression and activity in breast cancer (VSports app下载)

Christine E Edmonds (V体育官网) et al. Am J Nucl Med Mol Imaging. .

Abstract

The nuclear enzyme PARP1 plays a central role in sensing DNA damage and facilitating repair. Tumors with BRCA1/2 mutations are highly dependent on PARP1 as an alternative mechanism for DNA repair, and PARP inhibitors generate synthetic lethality in tumors with BRCA mutations, resulting in cell cycle arrest and apoptosis. Zhou et al. recently synthesized an (18)F-labeled PARP1 inhibitor ([(18)F]FluorThanatrace) for PET, and demonstrated high specific tracer uptake in a xenograft model of breast cancer [1]. In the current study, we characterize the level of baseline PARP expression and activity across multiple human breast cancer cell lines, including a BRCA1 mutant line. PARP expression and activity, as measured by levels of PAR and PARP1, is correlated with in vitro [(18)F]FluorThanatrace binding as well as tracer uptake on PET in a xenograft model of breast cancer. Radiotracer uptake in genetically-engineered mouse fibroblasts indicates [(18)F]FluorThanatrace is selective for PARP1 versus other PARP enzymes. This motivates further studies of [(18)F]FluorThanatrace as an in vivo measure of PARP1 expression and activity in patients who would benefit from PARP inhibitor therapy VSports手机版. .

Keywords: BRCA mutation; PARP1; breast cancer. V体育安卓版.

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Figures (V体育2025版)

Figure 1
Figure 1
[18F]FTT structure.
Figure 2
Figure 2
Western blot analysis of BRCA1, PAR, and PARP. Actin was used as a loading control. HCC1937 showed low expression of BRCA1 and confirmed the deleterious mutation in the BRCA1 gene. MDA-MB-231 and MCF-7 showed higher expression of BRCA1 compared to HCC1937. In addition, HCC1937 showed the highest expression of PAR and PARP compared with the other two cell lines.
Figure 3
Figure 3
A. PAR expression measured via chemiluminescent ELISA assay, and PARP1 measured via western blot analysis. B. [18F]FTT specific binding ratio (SBR) radiotracer in vitro binding assay in cancer cell lines. C. Correlation of PAR and PARP vs. [18F]FTT SBR. D. [18F]FTT radiotracer in vitro binding assay in cancer cell lines.
Figure 4
Figure 4
[18F]FluorThanatrace-PET-CT images of tumor xenografts, with tumors implanted in the subcutaneous posterior back/shoulder region, marked by arrows. Coronal slices through the tumor bed for: A. MDA-MB 231; B. MCF7; and C. HCC 1937 xenografts; D. HCC 1937 xenograft pretreated 30 min prior to imaging with 50 mg/kg olaparib, IP.
See this image and copyright information in PMC

References (V体育官网)

    1. Zhou D, Chu W, Xu J, Jones LA, Peng X, Li S, Chen DL, Mach RH. Synthesis, [18F] radiolabeling, and evaluation of poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors for in vivo imaging of PARP-1 using positron emission tomography. Bioorg Med Chem. 2014;22:1700–1707. - VSports手机版 - PMC - PubMed
    1. Hassa PO, Hottiger MO. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. Front Biosci. 2008;13:3046–3082. - PubMed
    1. Thomas C, Tulin AV. Poly-ADP-ribose polymerase: machinery for nuclear processes. Mol Aspects Med. 2013;34:1124–1137. - PMC - PubMed
    1. Kameshita I, Matsuda Z, Taniguchi T, Shizuta Y. Poly (ADP-Ribose) synthetase. Separation and identification of three proteolytic fragments as the substrate-binding domain, the DNA-binding domain, and the automodification domain. J Biol Chem. 1984;259:4770–4776. - "V体育ios版" PubMed
    1. Tangutoori S, Baldwin P, Sridhar S. PARP inhibitors: A new era of targeted therapy. Maturitas. 2015;81:5–9. - PubMed

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