Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics

0543918 - ÚJF 2022 RIV DE eng J - Journal Article
Gilpin, I. M. F. - Ullrich, M. - Wunsche, T. - Zarschle, K. - Lebeda, Ondřej - Pietzsch, J. - Pietzsch, H. -J. - Walther, M.
Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics.
ChemMedChem. Roč. 16, č. 17 (2021), s. 2645-2649. ISSN 1860-7179. E-ISSN 1860-7187
Institutional support: RVO:61389005
Keywords : Bispidine * Mercury * Organomercury * Radiopharmaceuticals * Theranostics
OECD category: Pharmacology and pharmacy
Impact factor: 3.540, year: 2021
Method of publishing: Open access
https://doi.org/10.1002/cmdc.202100131

We show the synthesis of an in vivo stable mercury compound with functionality suitable for radiopharmaceuticals. The designed cyclic bisarylmercury was based on the water tolerance of organomercurials, higher bond dissociation energy of Hg-Ph to Hg-S, and the experimental evidence that acyclic structures suffer significant cleavage of one of the Hg-R bonds. The bispidine motif was chosen for its in vivo stability, chemical accessibility, and functionalization properties. Radionuclide production results in (HgCl2)-Hg-197(m)(aq), so the desired mercury compound was formed via a water-tolerant organotin transmetallation. The Hg-bispidine compound showed high chemical stability in tests with an excess of sulfur-containing competitors and high in vivo stability, without any observable protein interaction by human serum assay, and good organ clearance demonstrated by biodistribution and SPECT studies in rats. In particular, no retention in the kidneys was observed, typical of unstable mercury compounds. The Hg-nat analogue allowed full characterization by NMR and HRMS.
Permanent Link: http://hdl.handle.net/11104/0321959