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. Ga-68 or Lu-177). Moreover, the radionuclide Au-198 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 Ga-68, Lu-177 and Au-198.Results: New heterometallic gold metallacages of composition [M{Au(L-morph-kappa S)}(3)] (M = La3+, Tb3+, Lu3+ or Y3+) and [Ga{Au(L-morph-kappa S)}(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, H-1 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 mu M for [Ga{Au(L-diethyl)}(2)]NO3 on PC-3. The radiolabeling experiments thereof show high radiochemical purities with Ga-68 and Au-198 and low radiochemical purity with Lu-177.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.