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

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. (68)Ga or (177)Lu). Moreover, the radionuclide (198)Au 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 (68)Ga, (177)Lu and (198)Au. RESULTS: New heterometallic gold metallacages of composition [M{Au(L(morph)-κS)}(3)] (M = La(3+), Tb(3+), Lu(3+) or Y(3+)) and [Ga{Au(L(morph)-κS)}(2)]NO(3) have been synthesized from 2,6-dipicolinoylbis(N,N-morpholinylthiourea) (H(2)L(morph)) with [AuCl(THT)] and the target M(3+) metal ions in yields ranging from 33 (Lu) to 62% (Tb). The characterization of the compounds bases on ESI–MS, (1)H NMR, IR, EA and single-crystal X-ray diffraction techniques (all except the Ga derivative). Selected gold cages derived from H(2)L(morph) were compared to previously reported gold cages that were derived from 2,6-dipicolinoylbis(N,N-diethylthiourea) (H(2)L(diethyl)). The tested metallacages show similar IC(50) 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(L(diethyl))}(2)]NO(3) on PC-3. The radiolabeling experiments thereof show high radiochemical purities with (68)Ga and (198)Au and low radiochemical purity with (177)Lu. 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-023-00225-z.