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

Abstract

AuIII 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 AuIII‐NHC complexes by direct oxidation with radioactive [124I]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 AuIII‐to‐AuI reduction to achieve full anticancer activity, in vivo studies reveal that a fraction of the AuIII‐NHC prodrug is not immediately reduced after administration but able to reach the major organs before metabolic activation.

4,4,16‐Trifluoropalmitate: Design, Synthesis, Tritiation, Radiofluorination and Preclinical PET Imaging Studies on Myocardial Fatty Acid Oxidation

“…New tracers require careful assessment of in vivo metabolism, as the formation of labelled metabolites complicates image interpretation and quantification [53] . Hence, we first explored blood clearance and tracer's metabolism in vivo using an in‐house developed monitoring system (Figure 6a) as previously described [54] . The system allows for the real‐time determination of the concentration of radioactivity in arterial blood by extracorporeal circulation.…”

“…[53] Hence, we first explored blood clearance and tracer's metabolism in vivo using an inhouse developed monitoring system ( Figure 6a) as previously described. [54] The system allows for the real-time determination of the concentration of radioactivity in arterial blood by extracorporeal circulation. Additionally, blood samples were withdrawn at preselected time points (5, 10, 15 and 30 min) for further processing.…”

Current Developments of N-Heterocyclic Carbene Au(I)/Au(III) Complexes toward Cancer Treatment

“…An unexpected biochemical pathway can take place, contributing to in vivo Au(III) formation; Au(III) may form in vivo in case of oxidation by hypochlorite or myeloperoxidase after the intravenous injection of an Au(I) drug [ 27 ]. A recent insight on radiolabeled Au(III)-NHC complexes’ biodistribution was given by Salassa et al: [ 124 I]Au(III) complexes rapidly distributed through the blood stream and Au(III) accumulated in liver, kidneys, and lungs in higher concentrations comparing to brain, bladder and stomach; overtime, but not instantaneously, they reduced to Au(I) [ 51 ].…”

“…Besides the aforementioned target molecules, several studies underline their activity against other enzymes like cysteine proteases [ 41 ], aquaporins [ 42 ], protein tyrosine phosphatase [ 43 ], caspases [ 44 , 45 ], apoptosis inducing factor, and zinc finger [ 46 ]. As this review mainly addresses NHC Au(I)/(III) complexes for anticancer treatment, we refer the reader to additional review articles addressing the antimicrobial [ 47 , 48 ], antimalarial [ 49 ], anti-inflammatory [ 50 ], antioxidant [ 50 , 51 ], antileishmanial [ 50 , 52 ] and antiparasitic [ 53 ] activity of gold NHC complexes.…”

Anticancer Gold(III) Compounds With Porphyrin or N-heterocyclic Carbene Ligands

“…In addition to the tetradentate porphyrin ligands, stabilization of the gold(III) ion can also be achieved by coordination with the tridentate (C ∧ N ∧ C, C ∧ N ∧ N or N ∧ C ∧ N) pincer ligand containing deprotonated C-donor atom(s) (C − ) and/or neutral σ-donating N-heterocyclic carbene (NHC) ligand(s), affording gold(III) complexes with high physiological stability and promising anticancer properties (Bertrand et al, 2017;Carboni et al, 2018;Bauer et al, 2019;Fares et al, 2020;Guarra et al, 2020). In this context, we have described the antitumor-active…”