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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Ian Moore F. Gilpin - , Fakultät Chemie u. Lebensmittelchemie, Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Martin Ullrich - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Thomas Wünsche - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Kristof Zarschler - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Ondřej Lebeda - , Nuclear Physics Institute of the CAS (Autor:in)
  • Jens Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf, Technische Universität Dresden (Autor:in)
  • Hans Jürgen Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Martin Walther - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)

Abstract

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 197(m)HgCl2(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 natHg analogue allowed full characterization by NMR and HRMS.

Details

OriginalspracheEnglisch
Seiten (von - bis)2645-2649
Seitenumfang5
FachzeitschriftChemMedChem
Jahrgang16
Ausgabenummer17
PublikationsstatusVeröffentlicht - 6 Sept. 2021
Peer-Review-StatusJa

Externe IDs

PubMed 33949125

Schlagworte

Schlagwörter

  • Bispidine, Mercury, Organomercury, Radiopharmaceuticals, Theranostics