{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:05:53Z","timestamp":1787616353783,"version":"build-2736575974"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to improve the biodistribution of probes and enhance tumor targeting through <jats:sup>68<\/jats:sup>Ga\/<jats:sup>177<\/jats:sup>Lu-labeled optimized probes, thereby providing better tumor detection and assessment in PET imaging while also exploring their therapeutic effects on tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The physicochemical properties of PARPi probes were optimized through polyethylene glycol (PEG) modification. The tumor inhibition effect of the novel probes was validated through the assessment of <jats:italic>in vitro<\/jats:italic> affinity, uptake, <jats:italic>in vivo<\/jats:italic> distribution, and tumor targeting of the PARPi probes. Based on the distribution results, OLINDA\/EXM radiation dose estimation was then performed to optimize the clinically administered dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the study, a novel PARP-targeted imaging agent, DOTA-PEG-PARPi, was designed and optimized, demonstrating sufficient <jats:italic>in vivo<\/jats:italic> stability. The results of <jats:italic>in vitro<\/jats:italic> trials showed strong affinity and uptake of PEG-PARPi in pancreatic cancer tumor cells. SPECT\/CT imaging revealed significant radioactive accumulation, notable uptake, and prolonged retention time in PSN-1 tumors. Tissue distribution results showed that tumor uptake peaked 3\u00a0h after administration. According to dose estimation, the highest absorbed dose was observed in the pancreas of female adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The PEG-modified PARPi probe not only retained high affinity and targeting capability but also significantly improved retention time during <jats:italic>in vivo<\/jats:italic> trials.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1576587","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T05:30:25Z","timestamp":1747287025000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Preclinical studies of a PARP-targeted theranostic radiopharmaceutical for pancreatic cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Jie","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengya","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/s41416-023-02326-7","article-title":"PARP inhibitors: enhancing efficacy through rational combinations","volume":"129","author":"Bhamidipati","year":"2023","journal-title":"Br. 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