Academic Journal
Capturing Mercury-197m/g for Auger Electron Therapy and Cancer Theranostic with Sulfur-Containing Cyclen-Based Macrocycles
| العنوان: | Capturing Mercury-197m/g for Auger Electron Therapy and Cancer Theranostic with Sulfur-Containing Cyclen-Based Macrocycles |
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| المؤلفون: | Tosato M., Randhawa P., Asti M., Hemmingsen L. B. S., O'Shea C. A., Thaveenrasingam P., Sauer S. P. A., Chen S., Graiff C., Menegazzo I., Baron M., Radchenko V., Ramogida C. F., Di Marco V. |
| المساهمون: | Tosato, M., Randhawa, P., Asti, M., Hemmingsen, L. B. S., O'Shea, C. A., Thaveenrasingam, P., Sauer, S. P. A., Chen, S., Graiff, C., Menegazzo, I., Baron, M., Radchenko, V., Ramogida, C. F., Di Marco, V. |
| بيانات النشر: | AMER CHEMICAL SOC |
| سنة النشر: | 2024 |
| المجموعة: | Padua Research Archive (IRIS - Università degli Studi di Padova) |
| مصطلحات موضوعية: | mercury, chelator, radiopharmacy |
| الوصف: | The interest in mercury radioisotopes, Hg-197m (t(1/2) = 23.8 h) and Hg-197g (t(1/2) = 64.14 h), has recently been reignited by the dual diagnostic and therapeutic nature of their nuclear decays. These isotopes emit gamma-rays suitable for single photon emission computed tomography imaging and Auger electrons which can be exploited for treating small and metastatic tumors. However, the clinical utilization of Hg-197m/g radionuclides is obstructed by the lack of chelators capable of securely binding them to tumor-seeking vectors. This work aims to address this challenge by investigating a series of chemically tailored macrocyclic platforms with sulfur-containing side arms, namely, 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), and 1,7-bis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,10-diacetic acid (DO2A2S). 1,4,7,10-Tetrazacyclododecane-1,4,7,10-tetracetic acid (DOTA), the widest explored chelator in nuclear medicine, and the nonfunctionalized backbone 1,4,7,10-tetrazacyclododecane (cyclen) were considered as well to shed light on the role of the sulfanyl arms in the metal coordination. To this purpose, a comprehensive experimental and theoretical study encompassing aqueous coordination chemistry investigations through potentiometry, nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, and density functional theory (DFT) calculations, as well as concentration- and temperature-dependent [Hg-197m/g]Hg2+ radiolabeling and in vitro stability assays in human serum was conducted. The obtained results reveal that the investigated chelators rapidly complex Hg2+ in aqueous media, forming extremely thermodynamically stable 1:1 metal-to-ligand complexes with superior stabilities compared to those of DOTA or cyclen. These complexes exhibited 6- to 8-fold coordination environments, with donors statically bound to the metal center, as evidenced by the presence of H-1-Hg-199 spin-spin ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/39024562; info:eu-repo/semantics/altIdentifier/wos/WOS:001272797300001; volume:63; issue:30; firstpage:14241; lastpage:14255; numberofpages:15; journal:INORGANIC CHEMISTRY; https://hdl.handle.net/11577/3520361 |
| DOI: | 10.1021/acs.inorgchem.4c02418 |
| الاتاحة: | https://hdl.handle.net/11577/3520361 https://doi.org/10.1021/acs.inorgchem.4c02418 https://pubs.acs.org/doi/10.1021/acs.inorgchem.4c02418 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.A055225 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.inorgchem.4c02418 |
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