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. 2023 Nov 20;8(1):40.
doi: 10.1186/s41181-023-00225-z.

Metallacages with 2,6-dipicolinoylbis(N,N-dialkylthioureas) as novel platforms in nuclear medicine for 68Ga, 177Lu and 198Au

Anna Baitullina  1 , Guilhem Claude  1 , Suelen F Sucena  1 , Eda Nisli  2 , Cedric Scholz  1 , Punita Bhardwaj  2 , Holger Amthauer  2 , Winfried Brenner  2 , Christopher Geppert  3 , Christian Gorges  3 , Ulrich Abram  1 , Pedro Ivo da Silva Maia  4 , Sarah Spreckelmeyer  5
Affiliations

Metallacages with 2,6-dipicolinoylbis(N,N-dialkylthioureas) as novel platforms in nuclear medicine for 68Ga, 177Lu and 198Au

Anna Baitullina et al. EJNMMI Radiopharm Chem. .

Abstract

Background: Heterometallic gold metallacages are of great interest for the incorporation of several cations. Especially in nuclear medicine, those metallacages can serve as a platform for radionuclides relevant for imaging or therapy (e.g. 68Ga or 177Lu). Moreover, the radionuclide 198Au is an attractive beta emitter, for potential application in nuclear medicine. Here, we aim to synthesize a new set of gold metallacages and to study their ability to coordinate to 68Ga, 177Lu and 198Au.

Results: New heterometallic gold metallacages of composition [M{Au(Lmorph-κS)}3] (M = La3+, Tb3+, Lu3+ or Y3+) and [Ga{Au(Lmorph-κS)}2]NO3 have been synthesized from 2,6-dipicolinoylbis(N,N-morpholinylthiourea) (H2Lmorph) with [AuCl(THT)] and the target M3+ metal ions in yields ranging from 33 (Lu) to 62% (Tb). The characterization of the compounds bases on ESI-MS, 1H NMR, IR, EA and single-crystal X-ray diffraction techniques (all except the Ga derivative). Selected gold cages derived from H2Lmorph were compared to previously reported gold cages that were derived from 2,6-dipicolinoylbis(N,N-diethylthiourea) (H2Ldiethyl). The tested metallacages show similar IC50 values close to that of auranofin in four different cancer cell lines (MCF-7, PC-3, U383, U343), e.g. 4.5 ± 0.7 µM for [Ga{Au(Ldiethyl)}2]NO3 on PC-3. The radiolabeling experiments thereof show high radiochemical purities with 68Ga and 198Au and low radiochemical purity with 177Lu.

Conclusions: The results indicate that these gold metallacages could serve as a novel platform for inclusion of different (radio)nuclides with potential theranostic applications in nuclear medicine.

Keywords: Cancer; Heterometallic complexes; Metal complexes; Metals in medicine; Radiopharmaceuticals.

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Conflict of interest statement

SS is an Associate Editor of EJNMMI Radiopharmacy and Chemistry. All other declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
A Structure of the 2,6-dipicolinoylbis(N,N-dialkylthiourea) ligands used in this work, B, C gold(I) metallacages centered with M3+ ions
Fig. 2
Fig. 2
A Molecular structure of the complex [Lu{Au(Lmorph-κS)}3], as representative for the [M{Au(Lmorph-κS)}3]-type complexes. The hydrogen atoms and solvent molecules were omitted for clarity. B The coordination polyhedron around the Lu3+ metal center in [Lu{Au(Lmorph-κS)}3]. The nitrogen atoms are in green and oxygen atoms are in blue
Fig. 3
Fig. 3
Radio-chromatogram of the reaction between H2Ldiethyl, [AuCl(THT)] and 68Ga in methanol/Na-acetate after 10 min of incubation time
Fig. 4
Fig. 4
Radio-chromatogram of the reaction between H2Lmorph, [AuCl(THT)] and 68Ga in methanol and sodium acetate after 10 min
Fig. 5
Fig. 5
iTLC-chromatograms of stability assessment A [68Ga][Ga{Au(Ldiethyl)}2)]+ alone B [68Ga][Ga{Au(Ldiethyl)}2)]+ with human serum albumin
Fig. 6
Fig. 6
Radio-chromatogram of [198Au][Ga{Au(Ldiethyl)}2]+
Fig. 7
Fig. 7
A UV-chromatogram of [natLu{Au(Ldiethyl)}3], B radio-HPLC chromatogram [177Lu][Lu{Au(Ldiethyl)}3]
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