Affiliation:
1. Department of Chemistry Simon Fraser University 8888 University Drive V5A 1S6 Burnaby British Columbia Canada
2. Life Sciences Division TRIUMF 4004 Wesbrook Mall V6T 2A3 Vancouver British Columbia Canada
3. Department of Chemical Sciences University of Padova via Marzolo 1 35131 Padova Italy
4. Department of Chemistry University of Manitoba 140 Dysart Rd R3T 2N2 Winnipeg Manitoba Canada
5. Institute of Fundamental and Frontier Sciences University of Electronic Science and Technology of China 610054 Chengdu Sichuan P. R. China
6. Department of Chemistry University of British Columbia 2036 Main Mall V6T 1Z1 Vancouver British Columbia Canada
Abstract
AbstractMercury‐197 m/g are a promising pair of radioactive isomers for incorporation into a theranostic as they can be used as a diagnostic agent using SPECT imaging and a therapeutic via Meitner‐Auger electron emissions. However, the current absence of ligands able to stably coordinate 197m/gHg to a tumour‐targeting vector precludes their use in vivo. To address this, we report herein a series of sulfur‐rich chelators capable of incorporating 197m/gHg into a radiopharmaceutical. 1,4,7,10‐Tetrathia‐13‐azacyclopentadecane (NS4) and its derivatives, (2‐(1,4,7,10‐tetrathia‐13‐azacyclopentadecan‐13‐yl)acetic acid (NS4‐CA) and N‐benzyl‐2‐(1,4,7,10‐tetrathia‐13‐azacyclopentadecan‐13‐yl)acetamide (NS4‐BA), were designed, synthesized and analyzed for their ability to coordinate Hg2+ through a combination of theoretical (DFT) and experimental coordination chemistry studies (NMR and mass spectrometry) as well as 197m/gHg radiolabeling studies and in vitro stability assays. The development of stable ligands for 197m/gHg reported herein is extremely impactful as it would enable their use for in vivo imaging and therapy, leading to personalized treatments for cancer.
Funder
Natural Sciences and Engineering Research Council of Canada
Canadian Cancer Society Research Institute
Canadian Institutes of Health Research
National Research Council Canada
Subject
General Chemistry,Catalysis,Organic Chemistry
Cited by
3 articles.
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