Selective Chelation of the Exotic Meitner-Auger Emitter Mercury-197 m/g with Sulfur-Rich Macrocyclic Ligands: Towards the Future of Theranostic Radiopharmaceuticals.
Parmissa RandhawaK Lexi Gower-FryCailum M K StienstraMarianna TosatoShaohuang ChenYang GaoAnthony W McDonaghValerio Di MarcoValery RadchenkoGeorg SchreckenbachCaterina F RamogidaPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2023)
Mercury-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/g Hg 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/g Hg into a radiopharmaceutical. 1,4,7,10-Tetrathia-13-azacyclopentadecane (NS 4 ) and its derivatives, (2-(1,4,7,10-tetrathia-13-azacyclopentadecan-13-yl)acetic acid (NS 4 -CA) and N-benzyl-2-(1,4,7,10-tetrathia-13-azacyclopentadecan-13-yl)acetamide (NS 4 -BA), were designed, synthesized and analyzed for their ability to coordinate Hg 2+ through a combination of theoretical (DFT) and experimental coordination chemistry studies (NMR and mass spectrometry) as well as 197m/g Hg radiolabeling studies and in vitro stability assays. The development of stable ligands for 197m/g Hg reported herein is extremely impactful as it would enable their use for in vivo imaging and therapy, leading to personalized treatments for cancer.
Keyphrases
- high resolution
- fluorescent probe
- mass spectrometry
- aqueous solution
- living cells
- dengue virus
- photodynamic therapy
- fluorescence imaging
- magnetic resonance
- case control
- papillary thyroid
- liquid chromatography
- zika virus
- squamous cell carcinoma
- cancer therapy
- bone marrow
- ms ms
- current status
- high performance liquid chromatography
- capillary electrophoresis
- young adults
- single cell
- molecular dynamics simulations