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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1576587
This article is part of the Research Topic Development and Validation of New Molecular Probes of Nuclear Medicine and New Targets of Nuclear Drugs in Cancers View all articles
Preclinical studies of a PARP targeted theranostic radiopharmaceutical for pancreatic cancer
Provisionally accepted- 1 China Institute for Radiation Protection, Tauyuan, China
- 2 China Institute of Atomic Energy, Beijing, Beijing, China
- 3 First Hospital of Shanxi Medical University, Taiyuan, Shaanxi, China
- 4 China Isotope & Radiation Corporation, Beijing, China
Objective: This study aims to improve biodistribution of the probes, and enhance tumor targeting through 68 Ga/ 177 Lu-labeled optimized probes, thereby providing better tumor detection and assessment in PET imaging, while also exploring its therapeutic effects on tumors.The physicochemical properties of PARPi probes was optimized by using polyethylene glycol (PEG) modification. The tumor inhibition effect of the novel probes was validated through the assessment of in vitro affinity, uptake, in vivo distribution, and tumor targeting of the PARPi probes. Based on the distribution results, OLINDA/EXM radiation dose estimation was then performed to optimize the clinical administered dose.Results: In the study, a novel PARP-targeted imaging agent, DOTA-PEG-PARPi, was designed and optimized, demonstrating sufficient in vivo stability. The results of in vitro trials showed strong affinity and uptake of PEG-PARPi in pancreatic cancer tumor cells. SPECT/CT imaging revealed significant radioactive accumulation, notable uptake, and long retention time in PSN-1 tumors. Tissue distribution results founded that tumor uptake peaked at 3 hours after administration. According to dose estimation， the highest absorbed dose was observed in the pancreas of female adults.The PEG-modified PARPi probe not only retained high affinity and targeting capability but also significantly improved retention time during in vivo trials.
Keywords: PARPi, radioactive probes, Pancreatic Cancer, preclinical studies, Radiopharmaceutical
Received: 14 Feb 2025; Accepted: 17 Mar 2025.
Copyright: © 2025 Gao, Wang, Wang, Liu, Wang, Li and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jin Du, China Institute of Atomic Energy, Beijing, 275, Beijing, China
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