99mTc-labeling of ciprofloxacin and nitrofuryl thiosemicarbazone using fac-[99mTc(CO)3(H2O)3] core: evaluation of their efficacy as infection imaging agents

Abstract

The aim of this study was to radiolabel ciprofloxacin (Cip) and nitrofuryl thiosemicarbazone (NFT) with the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) core and to evaluate the ability of the radiopharmaceuticals as tracers in detecting sites of infection. Cip and NFT were radiolabeled with the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) core and characterized by RHPLC. The stabilities of the preparations were evaluated in saline and rat serum. In vitro binding studies of the radiopharmaceuticals with S. aureus were performed. Biodistribution studies were conducted at different time points after injecting (i.v.) the radiopharmaceuticals in rats (intramuscularly infected with S. aureus) as well as in rats with sterile inflammation. To assess the infection targeting capacity of (99m)Tc-tricarbonyl ciprofloxacin and nitrofuryl thiosemicarbazone, (99m)Tc(v)O-Cip and (99m)Tc(v)O-NFT were used as control. Scintigraphic imaging studies of tricarbonyl compounds and (99m)Tc(v)O-Cip were performed at 4 h after injection. The radiochemical purities of (99m)Tc(CO)(3)-Cip and (99m)Tc(CO)(3)-NFT were between 97-98% as determined by thin layer chromatography (TLRC) and RHPLC; no further purification is necessary before injection. The radiopharmaceuticals exhibited substantial stability when incubated in isotonic saline and serum up to 24 h. Biodistribution studies showed maximum uptake in the infected rat thigh muscle at 4 h post injection and washing out at slower rate from the infected site than the oxo technetium chelate. The mean ratios of uptake in infected/non-infected thighs were 3.87:1, 3.41:1 and 3.17:1 for (99m)Tc(CO)(3)-Cip, (99m)Tc(CO)(3)-NFT and (99m)Tc(v)O-Cip respectively. During scintigraphic studies, infection sites appeared quite distinctly with (99m)Tc(CO)(3)-Cip and (99m)Tc(CO)(3)-NFT, comparable to the behaviour with (99m)Tc(v)O-Cip. These results encouraged us for further development of infection imaging radiopharmaceuticals based on the (99m)Tc-tricarbonyl core.

Highlights of the Latest Developments in Radiopharmaceuticals for Infection Imaging and Future Perspectives

“…Multiple antibiotics with a variety of mechanisms of action such as ciproflaxicin (7,8) and nitrofuryl thiosemicarbazone (7), fluoroquinolone (9), isoniazid (10), ofloxacin (11,12), cephalosporin (13), clindamycin (14), doxycycline (15), ceftizoxime (16,17), cefotaxime (18), tinidazole (19), sulfadiazine (20), tazobactam (21) and metronidazole (22) were radiolabeled with 99m Tc to enable SPECT imaging in the pre-clinical models of infection. The majority of the authors employed Sn(+2) salts as the reducing agents for 99m Tc which produced [ 99m Tc-O](3+) core, while in several publications 99m Tc carbonyl or [ 99m Tc-N](2+) cores were utilized (7,8,11). The smaller size of 99m Tc carbonyl core might be less perturbing to the molecular structure of antibiotic molecules.…”

Development of a peptide-based bifunctional chelator conjugated to a cytotoxic drug for the treatment of melanotic melanoma

“…The fac-[ 99m TcIJCO) 3 IJH 2 O) 3 ] + precursor was prepared as per the reported method. 28,29 Briefly, an aqueous solution (1.5 mL) containing Na/K tartrate (15 mg), Na 2 CO 3 (4 mg) and NaBH 4 (5.5 mg) was purged with carbon monoxide for 6-8 min at room temperature, followed by the addition freshly extracted aqueous 99m TcO 4 − (0.5 mL, 185-370 MBq), and the mixture was heated at 80°C for 20 min. The pH was adjusted between 6.5 and 7 with a mixture of 0.5 M phosphate buffer (pH 7.5) : 1 N HCl (1 : 3) and the purity of the tricarbonyl precursor was analysed by HPLC.…”

Physicochemical and Biological Study of 99mTc and 68Ga Radiolabelled Ciprofloxacin and Evaluation of [99mTc]Tc-CIP as Potential Diagnostic Radiopharmaceutical for Diabetic Foot Syndrome Imaging

“…They have a bactericidal effect and are therefore used to treat bacterial infections. The structure of quinolones allows various modifications to the molecule to be introduced without it losing its properties and therapeutic effect [13], so they are applied in radiopharmaceuticals for imaging bacterial infections after labelling with 99m Tc [11,[14][15][16][17][18] or 18 F [10,19,20].…”