124 I Radiolabeling of a AuIII -NHC Complex for In Vivo Biodistribution Studies

Federica Guarra; Alessio Terenzi; Christine Pirker; Rossana Passannante; Dina Baier; Ennio Zangrando; Vanessa Gómez-Vallejo; Tarita Biver; Chiara Gabbiani; Walter Berger; Jordi Llop; Luca Salassa

doi:10.1002/anie.202008046

¹²⁴ I Radiolabeling of a Au^III -NHC Complex for In Vivo Biodistribution Studies

Angew Chem Int Ed Engl. 2020 Sep 21;59(39):17130-17136. doi: 10.1002/anie.202008046. Epub 2020 Jul 29.

Authors

Federica Guarra¹, Alessio Terenzi^{2

3}, Christine Pirker⁴, Rossana Passannante⁵, Dina Baier^{4

6}, Ennio Zangrando⁷, Vanessa Gómez-Vallejo⁵, Tarita Biver^{1

8}, Chiara Gabbiani¹, Walter Berger⁴, Jordi Llop⁵, Luca Salassa^{2

9

10}

Affiliations

¹ Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124, Pisa, Italy.
² Donostia International Physics Center, Paseo M. Lardizabal 4, 20018, Donostia, Spain.
³ Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Viale delle Scienze, Ed. 17, 90128, Palermo, Italy.
⁴ Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, 1090, Vienna, Austria.
⁵ CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Paseo de Miramón 182, 20014, Donostia, Spain.
⁶ Institute of Inorganic Chemistry, Faculty of Chemistry University of Vienna, Waehringerstrasse 42, 1090, Vienna, Austria.
⁷ Department of Chemical and Pharmaceutical Sciences, University of Trieste, via Giorgieri 1, 34127, Trieste, Italy.
⁸ Department of Pharmacy, University of Pisa, via Bonanno 6, 56126, Pisa, Italy.
⁹ Kimika Fakultatea, Euskal Herriko Unibertsitatea, UPV/EHU, 20080, Donostia, Spain.
¹⁰ Ikerbasque, Basque Foundation for Science, 48013, Bilbao, Spain.

Abstract

Au^III complexes with N-heterocyclic carbene (NHC) ligands have shown remarkable potential as anticancer agents, yet their fate in vivo has not been thoroughly examined and understood. Reported herein is the synthesis of new Au^III -NHC complexes by direct oxidation with radioactive [¹²⁴ I]I₂ as a valuable strategy to monitor the in vivo biodistribution of this class of compounds using positron emission tomography (PET). While in vitro analyses provide direct evidence for the importance of Au^III -to-Au^I reduction to achieve full anticancer activity, in vivo studies reveal that a fraction of the Au^III -NHC prodrug is not immediately reduced after administration but able to reach the major organs before metabolic activation.

Keywords: N-heterocyclic carbenes; anticancer; metallodrugs; positron emission tomography; radiochemistry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Drug Screening Assays, Antitumor
Gold / chemistry
Gold / pharmacology*
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacology*
Humans
Iodine Radioisotopes
Ligands
Methane / analogs & derivatives*
Methane / chemistry
Methane / pharmacology
Mice
Molecular Structure
Positron-Emission Tomography
Tissue Distribution
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Heterocyclic Compounds
Iodine Radioisotopes
Iodine-124
Ligands
carbene
Gold
Methane