Abstract | INTRODUCTION:
Poly (ADP-ribose) polymerase-1 (PARP-1) plays many roles in prostate cancer (PC), such as mediating DNA damage repair, transcriptional regulation and nuclear hormone receptor signaling. Because of this, PARP-1 has been targeted for therapy in PC, and non-invasive imaging of PARP-1 could help predict which patients are likely to respond to such therapy. Several PARP-1 positron emission tomography (PET) imaging agents have been developed and show promise for imaging PARP-1 expression in breast, brain, and lung cancer in small animals, but not as yet in prostate cancer. [18F]WC-DZ-F is an analogue of [18F]FluorThanatrace (FTT) and [125I]KX1, which are well-established PARP-1 ligands for measuring PARP-1 expression. Herein, we evaluated the potential of [18F]WC-DZ-F for the imaging PARP-1 expression in PC. METHODS: [18F]WC-DZ-F was synthesized by a two-step sequence. [18F]WC-DZ-F was evaluated by in vitro uptake studies in PC-3 cells and by in vivo biodistribution and microPET imaging using PC-3 tumor xenografts. Ex vivo autoradiography of PC-3 tumors after microPET imaging was also performed. RESULTS: [18F]WC-DZ-F has high, PARP-1-specific uptake in PC-3 cells. In the microPET imaging study, [18F]WC-DZ-F accumulated in PC-3 xenograft tumors over 2 h, and the uptake was significantly reduced by blocking with olaparib. PC-3 tumors were clearly visualized in microPET images, and the imaging results were further confirmed by autoradiography of PC-3 tumors ex vivo. In the biodistribution study [18F]WC-DZ-F washed out quickly from most tissues within 2 h, except for the liver in which the uptake was not blockable by olaparib. CONCLUSIONS: We synthesized a novel PARP-1 radioligand, [18F]WC-DZ-F. The preliminary evaluation of [18F]WC-DZ-F indicates that it is a suitable PET imaging agent for measuring PARP-1 expression in prostate cancer and should be applicable to other types of cancers.
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Authors | Dong Zhou, Jinbin Xu, Cedric Mpoy, Wenhua Chu, Sung Hoon Kim, Huifangjie Li, Buck E Rogers, John A Katzenellenbogen |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 66
Pg. 26-31
(11 2018)
ISSN: 1872-9614 [Electronic] United States |
PMID | 30195072
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2018 Elsevier Inc. All rights reserved. |
Chemical References |
- Fluorine Radioisotopes
- Ligands
- Radiopharmaceuticals
- Poly (ADP-Ribose) Polymerase-1
- Fluorine-18
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Topics |
- Animals
- Autoradiography
- Cell Line, Tumor
- Fluorine Radioisotopes
- Gene Expression Regulation, Neoplastic
- Humans
- Isotope Labeling
- Ligands
- Male
- Mice
- Poly (ADP-Ribose) Polymerase-1
(metabolism)
- Positron-Emission Tomography
(methods)
- Prostatic Neoplasms
(diagnostic imaging, metabolism, pathology)
- Radiochemistry
- Radiopharmaceuticals
(chemistry, metabolism, pharmacokinetics)
- Tissue Distribution
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