EJNMMI radiopharmacy and chemistry · 2025
Synthesis and in vitro characterization of [198Au]Auranofin.
СтатьяНазвание и аннотация: Перевод в очереди
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Bhardwaj Punita, Frohner Caroline, Geppert Christopher, Gorges Christian, Brenner Winfried, Claude Guilhem, Spreckelmeyer Sarah
Аннотация
BACKGROUND: Radiopharmaceuticals offer targeted treatment by combining diagnostic or therapeutic radionuclides with biologically active molecules. Auranofin is the only Food and Drug Administration (FDA) approved gold(I) complex, originally developed for the treatment of rheumatoid arthritis. Recent evidence has highlighted its potential as an anticancer agent due to its ability to disrupt redox signaling, inhibit thioredoxin reductase, and impair glycolytic metabolism. This study aims to incorporate the true theranostic radionuclide 198Au into the Auranofin scaffold and evaluate its impact in-vitro on cancer cells.
RESULTS: Carrier-added (c.a.)198Au was produced via neutron activation of 197Au and subsequently converted into c.a. H [198Au] [AuCl₄]. Downscaled synthetic protocols were developed to sequentially generate c.a. [198Au] [Au(tht)Cl], [198Au] [Au(PEt₃)Cl], and [198Au]Auranofin. Radiochemical purity was evaluated using radio-high performance liquid chromatography, and in vitro stability was assessed in human serum albumin (HSA) over 72 h. Cytotoxic and metabolic activity were investigated in MCF7 and PC3 cancer cell lines using the cell viability assay 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and hexokinase assay, respectively. [198Au]Auranofin (c.a.) was obtained with a yield of 57.0 ± 3.2% and a radiochemical purity of 96.2 ± 3.9%. The compound demonstrated stability in human serum albumin, maintaining 96.9 ± 2.5% integrity over 72 h. In vitro studies revealed that c.a. [198Au]Auranofin exhibited enhanced cytotoxicity and significant hexokinase inhibition compared to its non-radioactive counterpart, while the precursor complexes remained non-toxic up to 20 µM. Viability loss was both concentration and radioactivity dependent across both cell lines.
CONCLUSIONS: [198Au]Auranofin (c.a.) represents a stable and effective radiogold-based radiopharmaceutical agent, offering redox-targeted cytotoxicity alongside β⁻ emission mediated cell death and γ emission based imaging potential. These findings highlight c.a. [198Au]Auranofin as a promising radiogold-based theranostic candidate, offering dual capabilities in targeted cytotoxicity and nuclear imaging. While the in vitro results are encouraging, further in vivo and translational studies are warranted to fully evaluate its clinical potential in nuclear medicine guided cancer therapy.
RESULTS: Carrier-added (c.a.)198Au was produced via neutron activation of 197Au and subsequently converted into c.a. H [198Au] [AuCl₄]. Downscaled synthetic protocols were developed to sequentially generate c.a. [198Au] [Au(tht)Cl], [198Au] [Au(PEt₃)Cl], and [198Au]Auranofin. Radiochemical purity was evaluated using radio-high performance liquid chromatography, and in vitro stability was assessed in human serum albumin (HSA) over 72 h. Cytotoxic and metabolic activity were investigated in MCF7 and PC3 cancer cell lines using the cell viability assay 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and hexokinase assay, respectively. [198Au]Auranofin (c.a.) was obtained with a yield of 57.0 ± 3.2% and a radiochemical purity of 96.2 ± 3.9%. The compound demonstrated stability in human serum albumin, maintaining 96.9 ± 2.5% integrity over 72 h. In vitro studies revealed that c.a. [198Au]Auranofin exhibited enhanced cytotoxicity and significant hexokinase inhibition compared to its non-radioactive counterpart, while the precursor complexes remained non-toxic up to 20 µM. Viability loss was both concentration and radioactivity dependent across both cell lines.
CONCLUSIONS: [198Au]Auranofin (c.a.) represents a stable and effective radiogold-based radiopharmaceutical agent, offering redox-targeted cytotoxicity alongside β⁻ emission mediated cell death and γ emission based imaging potential. These findings highlight c.a. [198Au]Auranofin as a promising radiogold-based theranostic candidate, offering dual capabilities in targeted cytotoxicity and nuclear imaging. While the in vitro results are encouraging, further in vivo and translational studies are warranted to fully evaluate its clinical potential in nuclear medicine guided cancer therapy.