Preliminary evaluation of a novel ¹⁸F-labeled PARP-1 ligand for PET imaging of PARP-1 expression in prostate cancer

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.