Influence of ligand denticity on the properties of novel 99mTc(I)–carbonyl complexes. Application to the development of radiopharmaceuticals for imaging hypoxic tissue

Bifunctional Metal – Nitroimidazole Complexes for Hypoxia Theranosis in Cancer

“…The HPLC profile of the Re analogue matched that of 99m Tc-IDA-NI. Other examples include ReNtm-1(11) and Re-Ntm-2 (12) (Figure 6), which were both prepared via ligand substitution on the precursor fac-[NEt4]2[Re(CO)3Br3] [44]. HPLC analyses and UV detection of the Re analogues showed main peaks with the same retention time as the corresponding 99m Tc complexes.…”

“…Its utility as a bifunctional chelator was explored by conjugating it with a series of nitroimidazole compounds (45-47; Figure 14) through a short alkyl chain and subsequent labelling with [ Copper-catalysed Huisgen cycloaddition or "click" reaction has been employed in the preparation of suitable bifunctional bidentate and tridentate ligands containing triazole moieties. In particular, 48 and 49 ( Figure 15) were designed and synthesized starting with the metronidazole, which was transformed to the corresponding azide via the Mitsunobu reaction using azidotrimethylsilane as the nucleophile or converting the -OH group to methylsulfonate followed by a substitution reaction with sodium azide [44]. The organic azide was then reacted with the corresponding alkyne, N-methylpropargylamine or propargylglycine using the CuSO4 and ascorbic acid catalytic system to form These ligands were labelled with 99m Tc(I)-tricarbonyl precursor to yield the desired complexes in high purity.…”

Neutral 99mTc(CO)3 complexes of “clicked” nitroimidazoles for the detection of tumor hypoxia

“…IR (neat, cm -1 ) 3121(m); 2918(w); 2853(w); 1545(s); 1406(s); 1044(s); 656(s). 1 General procedure for synthesis of nitroimidazole azides Bromide derivatives of different nitroimidazoles were converted into corresponding azides by reacting with NaN 3 in dimethylformamide [27]. Upon completion of the reaction the solvent was removed using rotary evaporator.…”

“…General procedure for synthesis of triazole from azide Different terminal nitroimidazole azides were converted into corresponding triazoles via ''click reaction'' with Lpropargyl glycine in presence of sodium ascorbate and copper sulphate in water [27]. The reaction mixture was kept stirring at room temperature for 36 h. It was subsequently washed with dichloromethane to remove excess nitroimidazole azide.…”

“…Nitroimidazoles which show selective accumulation in hypoxic cells are the most widely explored molecules for delineating hypoxic tumor cells from normoxic cells [10]. Several nitroimidazole radiopharmaceuticals based on PET as well as SPECT isotopes are reported [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Presently, [ 18 F]fluoromisonidazole ([ 18 F]FMISO), a 2-nitroimidazole-radiotracer, is the radiopharmaceutical of choice for clinical imaging of tumor hypoxia [29].…”