Poster Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Radiantly beautiful: Radioactive gallium and lutetium complexes as novel cancer theranostics (#472)

Sira Dahlhaus 1 , Vivien Michaelis 2 , Julia Bornhorst 2 , Fabian Mohr 1
  1. Inorganic Chemistry, University of Wuppertal, Wuppertal, NRW, Germany
  2. Food Chemistry, University of Wuppertal, Wuppertal, NRW, Germany

The use of radioisotopes in cancer therapy offers great potential for a selective and effective treatment approach.1-3 In this work, we report a family of gallium(III) and lutetium(III) complexes with pentadentate ligands containing a bis(semicarbazone)-framework (Figure 1). Their synthesis, structures and stability in solution was studied by various methods and in addition, we also examined their in vitro cytotoxicity in a human liver tumour cell line.

Starting from 2,6-diacetylpyridine, the ligands were prepared by a condensation reaction with various hydrazides. The resulting compounds readily react with methanolic or aqueous solutions of GaCl3 or Ga(NO3)3, forming the corresponding yellow gallium(III) complexes in high yields. Depending on the starting material, we isolated compounds of different stoichiometry, based on X-ray structure analysis. In the case of GaCl3 a monocationic dichlorido complex was formed, whereas with Ga(NO3)3 a bis(aqua) gallium trication was observed. In both cases however, the metal-ion is seven-coordinate with the ligands acting as neutral pentadentate N3,O2-donors (Figure 1). Using the same synthetic procedure, bis(aqua)nitrato lutetium(III) complexes were accessible using an aqueous solution of Lu(NO3)3 as metal-precursor. In this case, the lutetium has a coordination number of nine with a chelating nitrate ligand, two water molecules and the pentadentate hydrazide ligand.

The complexes were characterized by various methods including NMR spectroscopy, mass spectrometry and single crystal X-ray diffraction. Of particular relevance for biological studies is their stability in aqueous systems, which was monitored by UV-vis spectroscopy. The compounds were found to have no significant cytotoxic effect in HepG2 liver carcinoma cell lines, even at 50 mM concentrations. Work is currently underway to study formation and stability of analogues compounds containing the radioisotopes 68Ga and 177Lu.

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  1. C. R. Chitambar, Future Med. Chem., 2012, 4, 1257–1272.
  2. X. Peng, S. Gao, J. Zhang, Eur. J. Inorg. Chem., 2022, 6, e202100953.
  3. J. R. Dilworth, R. Hueting, Inorg. Chim. Acta, 2012, 389, 3-15.