Current Radiopharmaceuticals

Sean L. Kitson
Current Radiopharmaceuticals
Almac Sciences
Almac House
20 Seagoe Industrial Estate
Craigavon, BT63 5QD
Northern Ireland


Mixed Tridentate π -Donor and Monodentate π -Acceptor Ligands as Chelating Systems for Rhenium-188 and Technetium-99m Nitrido Radiopharmaceuticals

Author(s): Alessandra Boschi, Licia Uccelli, Micol Pasquali, Roberto Pasqualini, Remo Guerrini and Adriano Duatti

Affiliation: Laboratory of Nuclear Medicine, University of Ferrara, 44121 Ferrara, Italy.


A new molecular metallic fragment for labeling biologically active molecules with 99mTc and 188Re is described. This system is composed of a combination of tridentate π-donor and monodentate π-acceptor ligands bound to a [M Ξ N]2+ group (M = 99mTc, 188Re) in a pseudo square-pyramidal geometry. A simple structural model of the new metallic fragment was obtained by reacting the ligand 2, 2’-iminodiethanethiol [H2NS2 = NH(CH2CH2SH)2] and monodentate tertiary phosphines with the [M Ξ N]2+ group (M = 99mTc, 188Re). In the resulting complexes (dubbed3+1complexes), the tridentate ligand binds the [MΞN]2+ core through the two deprotonated, negatively charged, thiol sulfur atoms and the neutral, protonated, amine nitrogen atom. The residual fourth position of the five-coordinated arrangement is occupied by a phosphine ligand. The chemical identity of these model 99mTc and 188Re compounds was established by comparison with the chromatographic properties of the corresponding complexes obtained at the macroscopic level with the long–lived 99gTc and natural Re isotopes. The investigation was further extended to comprise a series of ligands formed by simple combinations of two basic amino acids or pseudo-amino acids to yield potential tridentate chelating systems having [S, N, S] and [N, N, S] as sets of π-donor atoms. Labeling yields and in vitro stability were investigated using different ancillary ligands. Results showed that SNS-type ligands afforded the highest labeling yields and the most robust 3+1 nitrido complexes with both 99mTc and 188Re. Thus, the new chelating system can be conveniently employed for labeling peptides and other biomolecules with the [MΞN]2+ group.

Keywords: Technetium-99m, rhenium-188, nitrido radiopharmaceuticals, 3+1 complexes, peptide chelators.

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Article Details

Page: [137 - 145]
Pages: 9
DOI: 10.2174/18744710113069990022