Syed Qaiser Shah

Radiosynthesis and biodistribution of 99mTc-rifampicin: A novel radiotracer for in-vivo infection imaging

(99m)Tc-rifampicin ((99m)Tc-RMP) a new radioantibiotic complex was synthesized specifically for the infection localization caused by methicillin-resistant Staphylococcus aureus (MRSA). The in-vitro radiochemical purity (RCP) yield, in-vivo biodistribution behavior in artificially infected rats (AIT) and scintigraphic accuracy in artificially infected rabbit (AIB) of the (99m)Tc-RMP complex was investigated using different concentration of the RMP, sodium pertechnetate (Na(99m)TcO(4)), stannous chloride dihydrate (SnCl(2) x 2H(2)O) at different pH ranges 5-6. The best RCP yield observed at 30, 60, 90 and 120 min after labeling was; 98.95+/-0.20, 98.15+/-0.24, 96.50+/-0.27 and 91.55+/-0.22%, respectively, using 1.5 mg RMP, 175 microL of SnCl(2) x 2H(2)O (1 microg/microL in 0.01 N HCl), 3 mCi of Na(99m)TcO(4), at pH 5.6. Initially in the infected muscle (INM) of the AIT the activity was lower but after 90 min it went up to 18.35+/-0.20% from 5.95+/-0.25%. The activity in the inflamed muscle (IMM), normal (NM) muscle, blood, liver and spleen was initially high that decreased with time. The ratios of the INM/NM and IMM/NM were 7.34+/-0.74 and 1.20+/-0.85, respectively. The whole body static (WBS) imaging of the MRSA infected rabbit confirmed the usefulness of the (99m)Tc-RMP as a precise radiotracer for MRSA infection imaging. On the basis of in-vitro RCP, in-vivo biodistribution and scintigraphic precision, we recommend the (99m)Tc-RMP complex prepared aseptically for in-vivo assessment of MRSA infection.

Radiosynthesis and biological evaluation of the 99mTc-tricarbonyl moxifloxacin dithiocarbamate complex as a potential Staphylococcus aureus infection radiotracer

In the present investigation, radiosynthesis of the (99m)Tc-tricarbonyl moxifloxacin dithiocarbamate complex ((99m)Tc(CO)(3)-MXND) and its biological evaluation in male Wister rats (MWR) artificially infected with Staphylococcus aureus (S. aureus) was assessed. The (99m)Tc(CO)(3)-MXND complex was radiochemically examined in terms of stability in saline and in serum and biologically its in-vitro binding with S. aureus and percent absorption in MWR models. Radiochemically the (99m)Tc(CO)(3)-MXND complex showed more than 90% stability in saline up to 240 min and in serum 14.95% undesirable species was appeared within 16h. In-vitro the (99m)Tc(CO)(3)-MXND complex showed saturated binding with S. aureus. In MWR artificially infected with live S. aureus the complex showed about six fold higher uptakes in the infected muscle as compared to the normal muscle. However, insignificant change in the uptake of (99m)Tc(CO)(3)-MXND complex in the infected and inflamed or normal muscle was observed in the MWR infected with heat killed S. aureus. The (99m)Tc(CO)(3)-MXND complex disappeared from the circulatory system and appeared in the urinary system within 60-90 min followed by excretion through normal route of urinary system. Based on the elevated and stable radiochemical succumb in saline, serum, saturated in-vitro binding with S. aureus and higher accumulation in the target organ of the MWR, we recommend the (99m)Tc(CO)(3)-MXND complex for radio-localization of the infection induced by S. aureus in human.

Phytochemical and antitrypanosomal investigation of the fractions and compounds isolated from Artemisia elegantissima.

Abstract Context: Trypanosoma brucei brucei (T.b. brucei) infection causes death in cattle, while the current treatments have serious toxicity problems. However, natural products can be used to overcome the problems associated with parasitic diseases including T.b. brucei. Objective: Artemisia elegantissima Pamp (Asteraceae) was evaluated phytochemically for its constituents and antitrypanosomal potential against T.b. brucei for the first time. Scopoletin isolated from A. elegantissima has shown better potential then the standard drug suramin, used against T.b. brucei. Materials and methods: The ethanol extract of the aerial parts of A. elegantissima was fractionated by column and preparative thin-layer chromatography into six fractions (A–F) yielding 13 compounds, these were evaluated for their antitrypanosomal activity against T.b. brucei at different concentrations. Results: Thirteen compounds were isolated from A. elegantissima: (Z)-p-hydroxy cinnamic acid, stigmasterol, β-sitosterol, betulinic acid, bis-dracunculin, dracunculin, scopoletin, apigenin, dihydroluteolin, scoparol, nepetin, bonanzin, and 3′,4′-dihydroxy bonanzin. The fractions D–F were found to be active at the concentration of 20 µg/ml and three compounds isolated from these fractions, scopoletin (MIC ≤0.19 µg/ml), 3′,4′-dihydroxy bonanzin (MIC = 6.25 µg/ml) and bonanzin (MIC = 20 µg/ml), were found to be highly active. Discussion and conclusion: Artemisia elegantissima was phytochemically and biologically explored for its antitrypanosomal potential against T.b. brucei. The number and orientation of phenolic hydroxyl groups play an important role in the antitrypanosomal potential of coumarins and flavonoids. The compounds 3′,4′-dihydroxy bonanzin and scopoletin with low MIC values, hold potential for use as antitrypanosomal drug leads.

(99m)Tc(CO)(3)-Ibritumomab tiuxetan; a novel radioimmunoimaging (RII) agent of B cell non-Hodgkin's lymphoma (NHL).

Abstract To exploit the B-lymphocyte antigen-CD20 binding capacity of the Ibritumomab tiuxetan (IBTN) monoclonal antibody (mAb) for imaging, the over-expression of B cells in non-Hodgkin’s lymphoma (NHL) (a myeloproliferative disorder of the lymphatic system) was investigated. In the current investigation, we present the labeling of the IBTN with technetium-99m (99mTc) through [99mTc(CO)3]+ precursor for radioimmunoimaging (RII) of the tumor prior to its treatment with 90Y labeled IBTN. Labeled IBTN was radiobiologically characterized in terms of radiochemical purity, in vitro stability in human plasma, immunoreactivity, binding with Raji and Ramos cells and biodistribution in a female nude mouse (FNM) model. It was observed that the reduced IBTN (rIBTN) showed more promising radiobiologic characteristics than the nonreduced IBTN. Significantly higher transchelation was seen in excess cysteine compared with histidine. The radioconjugate showed higher saturated binding affinity with CD20 antigen. Significantly higher target (tumor) to background ratios were observed 1 h post-injection (p.i.). Based on radiochemical purity, in vitro stability, immunoreactivity, binding and biodistrubtion in the FNM model, we recommend the radiolabeling of the rIBTN using tricarbonyl technique as a potential RII agent.

Imaging prostate cancer (PCa) with [99mTc(CO)3]finasteride dithiocarbamate

This investigation aimed to modify finasteride (1) to finasteride dithiocarbamate (2) for subsequent synthesis of the rhenium analogue (3) and [99m Tc]tricarbonyl complexes (4), to assess its prostate cancer (PCa) targeting potential in a rat model. To validate the identity of (4), reference (3) has been synthesized by using fac-[Net4 ]2 [ReBr3 (CO)3 ] precursor and characterized by 1 H-NMR, 13 C-NMR, ESI-MS, and elemental analysis. The analogue (4) was synthesized by using fac-[99m Tc(H2 O)3 (CO)3 ]+ precursor, and its structure was confirmed by comparative HPLC by using (3) as a reference. Further, the suitability of (4) as a PCa imaging agent was investigated in vitro and in vivo. At room temperature, (4) had ≥99% radiochemical purity and remained ≥84% stable in serum. In preclinical studies, biodistribution of (4) in histopathologically established rat model showed adequately high in vivo uptake in the prostate attracting the possibility of using it for noninvasive imaging of PCa.

Synthesis of (99m)TcN-clinafloxacin Dithiocarbamate Complex and Comparative Radiobiological Evaluation in Staphylococcus aureus Infected Mice.

Clinafloxacin dithiocarbamate (CNND) preparation and radiolabeling through [99mTc ≡ N]2+ core with the gamma (γ) emitter (99mTc) was assessed. The potentiality of the 99mTcV ≡ N-CNND complex was investigated as perspective a Staphylococcus aureus (S.a.) in vivo infection radiotracer in terms of radiochemical stability in normal saline (n.s.), human serum (h.s.), binding efficacy with live and heat killed S.a. and biodistribution in female nude mice model (FNMD). More than 90% stability was observed in n.s. for 4 h with the highest yield of 98.70 ± 0.26% at 30 min after reconstitution. In h.s., the 99mTcV ≡ N-CNND complex was found stable up to 16 h with 15.35% side products. Maximum in vitro binding (68.75 ± 0.80%, 90 min) with S.a. was observed after 90 min of incubation. In FNMD, (infected with live strain) approximately six-fold higher uptakes was noted in the infected to inflamed and normal muscles. The higher stability in n.s., h.s., higher S.a. (live) up take with specific and targeted in vivo distribution confirmed potentiality of the 99mTcV ≡ N-CNND complex as perspective S.a. in vivo infection radiotracer.

Synthesis and Biological Evaluation of the 99mtcn-Gemifloxacin Dithiocarbamate Complex: A Novel Streptococcus Pneumoniae Infection Imaging Agent

Synthesis and biological evaluation of the 99mTcN-Gemifloxacin dithiocarbamate (99mTcN-GIND) complex was investigated in terms of radiochemical stability (RCP) in saline, serum, in-vitro binding with Streptococcus pneumoniae (S. pneumoniae) and biodistribution in male Wistar rats artificially infected with living and heat killed S. pneumoniae. The maximum RCP was 98.25 ± 0.30% at 30 min and decreased to 91.25 ± 0.34% within 240 min. The complex showed stable behavior (in-vitro) in serum at 37°C with a 14.35% undesirable side products within 16 h. The complex showed 71.25% in-vitro binding S. pneumoniae. The uptake of the complex in the infected muscle was six times higher than the inflamed and normal muscles of the MWR infected with living S. pneumoniae. The promising (in-vitro and in-vivo) radiochemical and biological behavior posed the 99mTcN-GIND complex as a potential radiotracer for S. pneumoniae infection.

Synthesis of 99mTc(CO)3-Pazufloxacin Dithiocarbamate Complex and Biodistribution in Experimentally Induced Infection in Female Nude Mice

In this study the 99mTc(CO)3-PZND complex was prepared through the [99mTc(CO)3(H2O)3]+ technique and its radiobiological characteristics were compared with 99mTcV≡N-PZND complex in terms of stability in saline and in serum, in vitro Escherichia coli (E. coli) uptake and biodistribution in female nude mice model. Based on the elevated stability in saline, improved immovability in serum, higher in vitro E. coli uptake, and promising in vivo biodistribution, we confirmed the pre-eminence of the 99mTc(CO)3-PZND complex as a much better in vivo E. coli infection radiotracer than the 99mTcV≡N-PZND complex.