Synthesis and Evaluation of Technetium-99m (i) Tricarbonyl and Technetium-99m (v) oxo Chelates of Various amino, Carboxy and Thiol Based Ligand Systems: Utilization of this approach Towards the Development of Site Specific Radiopharmaceuticals.

Technetium-99m (99mTc) based radiopharmaceuticals have established themselves as a very important class of compounds in the diagnosis of various organ malfunction in computerized g-camera imaging. These types of radiopharmaceuticals are produced in many cases by chelating 99mTc with organic compounds having multifunctional electron rich groups which through coordination establish chemical bond with the metal. The complexes thus formed accommodate technetium in different oxidation states.The most stable and readily accessible oxidation states are often characterized by chemically robust core structures which may be exploited as platforms for the development of radiopharmaceutical reagents. The most extensively developed core structure is {Tc(V)O}3+, particularly with tetradentate ligands of the NxS(4-x) type. Past research has focused primarily on attachment of the bifunctional chelators for complexation of the {Tc(V)O}3+ core into small tripeptides and tetra-peptides. This has been accomplished predominantly using N3S and N4 ligands. Other structural subunits which have attracted attention include the {TcN}2+, {TcO2}+, and technetium 6-hydrazinonicotinic acid {Tc(HYNIC)x}3+ (where x = 1 or 2) cores. More recently, the Tc(I) core, technetium tricarbonyl {Tc(CO)3}+ has been shown to provide an ideal geometry for the labeling of chelators of the {Tc(CO)3}+ core with high specific activity

Development and Physical Characterization of Chloramphenicol Loaded Biodegradable Nanoparticles for Prolonged Release

The objectives of our study were to prepare a biodegradable nanoparticulate system of chloramphenicol (CHL) and to evaluate its ability to prolong in vitro release of CHL compared to free drug suspension (FDS). CHL-loaded polylactide-co-glycolide nanoparticles (CHL-PLGA-NPs) were prepared by an emulsion/solvent evaporation method using ethyl acetate and polyvinyl alcohol. CHL-PLGA-NPs were characterized by particle size, zeta potential, infrared spectra, drug entrapment efficiency and in vitro release kinetics measurement. Sonication was done with an ultrasound pulse sonicator at 70 W, 30 kHz for 60 s to produce stable NPs of mean size range from 277 nm to 433 nm. Drug to polymer ratio (D : P) was selected as formulation variable and significantly influenced entrapment efficiency (�30% to 66%) and release (p < 0.05). Entrapment of CHL in biodegradable NPs significantly prolonged drug release compared to FDS and thus implies potential antibiotic delivery system for ocular application

Chloramphenicol-Incorporated Poly Lactide-co-Glycolide (PLGA) Nanoparticles: Formulation, Characterization, Technetium-99m Labeling and Biodistribution Studies

Chloramphenicol-loaded (CHL) poly-D,L-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were prepared by emulsification solvent evaporation technique either by using polyvinyl alcohol (PVA) as emulsion stabilizer or polysorbate- 80 (PS-80) as surfactant and characterised by transmission electron microscopy, zeta-potential measurements. The NPs were radiolabeled with technetium-99m (99mTc) by stannous reduction method. Labeling conditions were optimised to achieve high-labeling efficiency, in vitro and in vivo (serum) stability. The labeled complexes also showed very low transchelation as determined by DTPA challenge test. Biodistribution studies of 99mTc-labeled complexes were performed after intravenous administration in mice. The CHL-loaded PLGA NPs coated with PS-80 exhibited relatively high brain uptake with comparatively low accumulation in bone marrow to that of free drug and CHL-loaded PLGA NPs (PVA, used as emulsion stabilizer) at 24 h post injection time period. This indicates the usefulness of the above delivery system for prolonged use of the antibiotic

99mTc-Labeling of Ciprofloxacin and Nitrofuryl Thiosemicarbazone Using Fac-[99mTc(CO)3(H2O)3] Core: Evaluation of Their Efficacy as Infection Imaging Agents

The aim of this study was to radiolabel ciprofloxacin (Cip) and nitrofuryl thiosemicarbazone (NFT) with the fac-[99mTc(CO)3(H2O)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-[99mTc(CO)3(H2O)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 99mTc-tricarbonyl ciprofloxacin and nitrofuryl thiosemicarbazone, 99mTc(V)O-Cip and 99mTc(V)O-NFT were used as control. Scintigraphic imaging studies of tricarbonyl compounds and 99mTc(V)O-Cip were performed at 4 h after injection. The radiochemical purities of 99mTc(CO)3-Cip and 99mTc(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 99mTc(CO)3-Cip, 99mTc(CO)3-NFT and 99mTc(V)O-Cip respectively. During scintigraphic studies, infection sites appeared quite distinctly with 99mTc(CO)3-Cip and 99mTc(CO)3-NFT, comparable to the behaviour with 99mTc(V)O-Cip. These results encouraged us for further development of infection imaging radiopharmaceuticals based on the 99mTc-tricarbonyl core

Evaluation of 99mTc(I)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection

The aim of this study was to develop 99mTc(CO)3-labeled fluoroquinolones as novel SPECT radiopharmaceuticals for imaging bacterial infection. Fluoroquinolones, e.g., ofloxacin (OFX), levofloxacin (LVX), lomefloxacin (LMX) and norfloxacin (NFX) were labeled with a fac-[99mTc(CO)3(H2O)3]+ precursor. The radiochemical purity of the radiopharmaceuticals exceeded 97% as determined by thin layer chromatography and HPLC. No further purification was necessary before injection. The Re(CO)3 complex of one of the fluoroquinolones (levofloxacin) was synthesized using [Re(CO)3(H2O)3]OTf and Re(CO)5Br precursors in separate experiments and characterized by IR, NMR and mass spectroscopic analysis. These studies revealed the formation of a single species in which the piperazinyl nitrogen and the –COOH group attached to the benzoxazine ring system of quinolone were involved in co-ordination to the Re(CO)3 core. The HPLC elution pattern and retention time of the Re(CO)3-LVX complex were comparable to those of the corresponding 99mTc(CO)3-complex proving their similarity. When incubated in isotonic saline and serum up to 24 h 99mTc(CO)3-labeled fluoroquinolones exhibited good in vitro stability. Biodistribution studies performed at different time points on rats intramuscularly infected with S. aureus as well as on rats with sterile inflammation revealed a higher uptake in the infected area than the turpentine induced inflamed area. The uptake in infected thigh was significant with 99mTc(CO)3-OFX followed by 99mTc(CO)3-LVX. The mean ratios of the uptake in infected/non-infected thighs were 4.75 and 4.27 at 8 h and 24 h, respectively, for 99mTc(CO)3-OFX and 4.42 and 4.18 at 24 h and 8 h, respectively, for 99mTc(CO)3-LVX. The above abscess to muscle ratios were higher than reported for 99mTc-ciprofloxacin and other 99mTc-labeled fluoroquinolones. Scintigraphy studies also showed a significant uptake in the infectious lesions suggesting that 99mTc(CO)3-fluoroquinolones might be useful as diagnostic agents for targeted delivery in bacterial infection

Preparation, Characterization, and Biodistribution of Letrozole Loaded PLGA Nanoparticles in Ehrlich Ascites Tumor Bearing Mice

Letrozole (LTZ) incorporated PLGA nanoparticles were prepared by solvent displacement technique and characterized by transmission electron microscopy, poly-dispersity index and zeta potential measurement. Radiolabeling of free LTZ and LTZ-loaded PLGA NPs was performed with technetium-99m with high labeling efficiency. The labeled complex showed good in vitro stability as verified by DTPA challenge test. The labeled complexes also showed significant in vivo stability when incubated in rat serum for 24 h. Biodistribution studies of 99mTc-labeled complexes were performed after intravenous administration in normal mice and Ehrlich Ascites tumor bearing mice. Compared to free LTZ, LTZ-loaded PLGA NPs exhibited significantly lower uptake by the organs of RES. The tumor concentration of LTZ-loaded PLGA NPs was 4.65 times higher than that of free LTZ at 4 h post-injection. This study indicates the capability of PLGA nanopartcles in enhancing the tumor uptake of letrozole

Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy

Non-steroidal anti-inflammatory drugs (NSAIDs) induce gastropathy by promoting mitochondrial pathology, oxidative stress, and apoptosis in gastric mucosal cells. We have synthesized SEGA (3a), a tryptamine-gallic acid hybrid, which prevents NSAID-induced gastropathy by preventing mitochondrial oxidative stress, dysfunction, and apoptosis. SEGA (3a) bears an immense therapeutic potential against NSAID-induced gastropathy. This novel molecule is a significant addition in the discovery of gastroprotective drugs

Tricarbonyltechnetium(I) and tricarbonylrhenium(I) complexes of amino acids: crystal and molecular structure of a novel cyclic dimeric Re(CO)3-amino acid complex comprised of the OON donor atom set of the tridentate ligand

Radiolabeled complexes of monoamino polycarboxylic, polyamino monocarboxylic and thiol containing amino acid ligands were prepared from a fac-[99mTc(CO)3(H2O)3]+ precursor.The overall radiochemical yield was 94–98%. The complexes exhibited substantial in vitro and in vivo stability. The corresponding Re(I) complexes of the ligands DAPA, Asp and CysH were prepared and characterized by means of IR, NMR, and MS spectroscopic studies, as well as X-ray crystallography (for those containing D,L-DAPA and D,L-Asp). The rhenium complexes have been structurally correlated with the technetium complexes by means of HPLC studies. The reaction of Re(CO)5Cl with D,L-Asp in presence of triethylamine led to the formation of a new class of cyclic dimeric complexes formed by the OON donor atom set of the tridentate ligands. The amino carboxylate ligand system formed well defined complexes with a fac-[M(CO)3(H2O)3]+ core and shows good promise in 99mTc(CO)3 tracer developmen