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(L^morph-κS)}₃] (M = La³⁺, Tb³⁺, Lu³⁺ or Y³⁺) and [Ga{Au(L^morph-κS)}₂]NO₃ have been synthesized from 2,6-dipicolinoylbis(N,N-morpholinylthiourea) (H₂L^morph) 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 H₂L^morph were compared to previously reported gold cages that were derived from 2,6-dipicolinoylbis(N,N-diethylthiourea) (H₂L^diethyl). 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(L^diethyl)}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.