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

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.