Subtype-selective positron emission tomography imaging of poly ADP-ribose polymerase-1 binding in non-human primates, healthy volunteers, and patients with glioblastoma using [11C]AZ14193391
Year: 2025
Type: article
Abstract: BACKGROUND: Poly ADP-ribose polymerase-1 (PARP1) is a key enzyme in DNA damage repair and an established target for cancer drug treatment. Although the emergence of non-invasive imaging of PARP using positron emission tomography (PET) has opened new opportunities in cancer diagnosis and drug development, subtype selective imaging of the enzyme, and particularly in brain, remains an unmet need. METHODS: The potent and selective novel PARP inhibitor AZ14193391 was labeled with carbon-11 and evaluated as a candidate PET radioligand for PARP1 through a series of translational in vitro and in vivo molecular imaging studies. These studies encompassed PET in non-human primates, healthy volunteers, and patients with glioblastoma. RESULTS: Robust radioligand binding to PARP1 was observed in the healthy non-human primate and human brain both in vitro and in vivo. Elevated tumor binding with high contrast was also demonstrated in patients with glioblastoma. CONCLUSIONS: The novel PET radioligand, [11C]AZ14193391 enables subtype selective imaging of PARP1 binding. Its ability to image this protein in the human brain paves the way for accelerated research, diagnosis and drug development in neuro-oncology.
Source: Neuro-Oncology
Authors: Zsolt Cselényi, Aurelija Jucaite, Giuseppe Stragliotto, Jiri Bartek, Peter Johnström, Andy Pike, Miguel A Cortés González, Antonia Högnäsbacka, Kenneth Dahl, Avipsa Ghosh, Jeffrey W Johannes, Anna D Staniszewska, Elisabetta Leo, Petra Hamerlik, Barry Davies, Sabina Cosulich, John Swales, Rachel Lawrence, Massimo Squatrito, Nancy Kathryn Mueller, Yasir Khani, Vasco C Sousa, Per Stenkrona, Christer Halldin, Lars Farde, Magnus Schou
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1302668884, G810223900
OpenAlex ID: W7117235459