^99mTc^I/Re^I Tricarbonyl Complexes with Tridentate Cysteamine Based Ligands: Synthesis, Characterization and in vitro/in vivo Evaluation

Abstract

Tricarbonyl MI (M = Re, 99mTc) complexes of a new tridentate cysteamine based chelator have been synthesized and fully characterized. To gain an insight into the usefulness of this new chelator for labeling biomolecules with a fac‐[M(CO)3]+ core, the ligand framework has been functionalized with a N‐(dialkylaminoalkyl) pharmacophore. The corresponding 99mTcI complexes showed moderate affinity for melanin and moderate cell uptake by B16F1 murine melanoma cells, and therefore deserve further evaluation in vivo as radioactive probes for the detection of melanomas.

Isostructural Re(i)/99mTc(i) tricarbonyl complexes for cancer theranostics

“…The dynamic behavior observed for Re1-Re4 is most probably due to the occurrence of pyramidal inversion at the coordinated sulfur atom, as we have previously observed for the congener Re(I) tricarbonyl complex with 2-(2-(ethylthio)ethylamino)acetic acid (herein designated as Re-(CO) 3 (NSO)). 22 These findings indicate that Re1-Re4 most probably contain ligands coordinated in a N,S,O-tridentate fashion, a coordination mode that was confirmed by X-ray diffraction analysis in the case of Re(CO) 3 (NSO). 23 In aqueous solution and at 100 °C, L1-L4 readily reacted with fac-[ 99m Tc(CO) 3 (OH 2 ) 3 ] + affording complexes Tc1-Tc4, respectively (Scheme 3).…”

“…21 Previously, we have shown that the cysteamine-based (S,N,O)-donor ligand 2-(2-(ethylthio)ethylamino)acetic acid affords low-molecular weight and lipophilic 99m Tc(I)/Re(I) complexes with high in vitro and in vivo stability. 22,23 We have anticipated that the replacement of the S-terminal ethyl substituent of this chelator by the 2-(4′aminophenyl)benzothiazole pharmacophore would not compromise the coordination capability of the (S,N,O)-donor set towards fac-[M(CO) 3 ] + (M = Re, 99m Tc) and the biological properties of the pharmacophore.…”

Synthesis, characterization, and in vitro evaluation of new coordination complexes of platinum(ii) and rhenium(i) with a ligand targeting the translocator protein (TSPO)

“…First discovered in 1994, 29 fac-[Re-(CO) 3 (OH 2 ) 3 ] + has proven to be an ideal cold model for developing the most suitable synthetic procedures to prepare 99m Tc as well as 188/186 Re radiopharmaceutical agents. 23,24,[30][31][32][33][34][35][36] For all synthesized compounds, in vitro studies have been performed to assess their affinity toward TSPO and their cytotoxic activity. In addition, platinum and rhenium cellular uptake (by ICP-MS), morphological analysis of the mitochondrion and of the nucleus (by fluorescence microscopy), as well as the ability of the newly synthesized compounds to cause collapse of the mitochondrial membrane potential (ΔΨ m ) and to interfere with the cell cycle progression of C6 glioma cells have been investigated.…”

Novel, Cysteine-Modified Chelation Strategy for the Incorporation of [MI(CO)3]+ (M = Re, 99mTc) in an α-MSH Peptide

“…26 However, the rhenium-sulfur bond in 4 was slightly shorter than observed in other ligands with thioether donors coordinated to fac -[Re I (CO) 3 ] + (2.455–2.504 Å). 25, 72 Similarly, the bond angles of the ligand relative to the metal observed in 4 (N Py -Re-NH 2 , 83.34(14)°; NH 2 -Re-S, 80.01(11)°; N Py -Re-S 79.83(10)°) were equally constricted as other five-membered coordination rings found with thioether pyridine ligands with fac -[Re I (CO) 3 ] + (N Py -Re-NH 2 , 82.0–85.26°; NH 2 -Re-S, 79.97–81.29°; N Py -Re-S, 79.23–80.52°). 26, 71 However, the N Py -Re-S angle in 4 was more restricted than the corresponding six-membered ring (88.93°) in a comparable fac -[Re I (CO) 3 ] + complex with S -(2-(2΄-pyridyl)ethyl)cysteamine.…”