Synthesis, characterization, and biological evaluation of new biotinylated ^99mTc/Re‐tricarbonyl complexes

Abstract

The synthesis and biological evaluation of three new biotinylated fac-[(99m)Tc/Re(CO)3](+) complexes with the tridentate ligands L1, L2, and L3 are reported. L1-L3 contain the chelators 2-((5-aminopentyl)(pyridin-2-ylmethyl)amino)acetic acid, 2-(2-aminoethylthio)-3-(1H-imidazol-4-yl)propanoic acid, and 2-amino-3-(1-carboxy-2-(1H-imidazol-4-yl)ethylthio)propanoic acid, respectively, which are conjugated to biotin's carboxylate via their amine group. The fac-[Re(CO)3(L1-L3)] complexes were synthesized and characterized by NMR and IR, where the (N,N,O) coordination for ReL1 and the (N,S,O) coordination for ReL2 and ReL3 were confirmed. The tracer complexes fac-[(99m)Tc(CO)3(L1-L3)] were synthesized in high yield and were found highly stable in 10(-3) M L-histidine and L-cysteine over 24 h. Furthermore, they exhibited high binding affinity (>90%) for avidin. Rat plasma studies showed complete cleavage of biotin from (99m)TcL1 after 1 h and a low percentage of intact (99m)TcL2 and (99m)TcL3 with no biotin cleavage metabolites present, over 24 h. Similarly, rat urine analysis showed the presence of intact (99m)TcL2 and (99m)TcL3, while (99m)TcL1 was cleaved. Biodistribution studies of (99m)TcL2 and (99m)TcL3 revealed fast blood and tissue clearance.

Synthesis and preliminary biological evaluation of a99mTc-chlorambucil derivative as a potential tumor imaging agent

“…This result concurs with the stability of the radiotracer in serum at 37°C in vitro . As reported in a previous study, another chlorambucil derivative was synthesized by conjugating an NNO chelating group [N‐(3‐(dimethylamino)propyl)amido]acetic acid to chlorambucil, which was further labeled with 99m Tc(CO) 3 successfully. The in vivo biological studies of the reported 99m Tc(CO) 3 ‐labeled chlorambucil derivative showed increasing uptake in the stomach with the time (increasing from 3.07% ID/g at 1 h to 17.7% ID/g at 3 h), indicating that this radiotracer took place an in vivo decomposition even though it was very stable (98% RCP) in vitro experimental study under 37°C incubation in PBS at pH 7.0 as well as in human serum .…”

“…The in vivo biological studies of the reported 99m Tc(CO) 3 -labeled chlorambucil derivative showed increasing uptake in the stomach with the time (increasing from 3.07% ID/g at 1 h to 17.7% ID/g at 3 h), indicating that this radiotracer took place an in vivo decomposition even though it was very stable (98% RCP) in vitro experimental study under 37°C incubation in PBS at pH 7.0 as well as in human serum. 20 The difference might originate from the different tridentate chelating moieties. In our study, the tridentate ligand 2,2′dipicolylamine (DPA) was chosen as the chelating scaffold, which exhibited favorable complexation property and kinetic stability with the fac-[M I (CO) 3 ] + core.…”

“…Chlorambucil (CLB) is a chemotherapy drug classified within the nitrogen mustard group, its mechanism of action involves alkylation, and has been used for the treatment of various malignancies . Moreover, it has also been used as a template to design drugs for diagnosis and therapy of tumors …”

“…15,16 Moreover, it has also been used as a template to design drugs for diagnosis and therapy of tumors. [17][18][19][20][21][22] In this study, a novel SPECT tumor imaging agent was synthesized on the basis of a design that combined the fac-[ 99m Tc(CO) 3 ] + core, CLB, and DPA. As a mimic of the 99m Tc-complex, the rhenium analog was also prepared using the same chemistry, and the purified complex was characterized by spectroscopic techniques.…”