Preparation and bioevaluation of 99mTc-carbonyl complex of 5-hydroxy tryptamine derivative.

Studies on the development of imaging agents for targeting neuroreceptors is an area of considerable interest owing to the limited availability of specific as well as selective radiolabeled agents. Therefore, with an aim of developing a receptor-specific agent, iminodiacetic acid (IDA) derivative of 5-hydroxy tryptamine viz., HTIDA has been synthesized. HTIDA could be radiolabeled with the synthon [(99m)Tc(CO)(3)(H(2)O)(3)](+) in >98% yield. The biodistribution studies in normal Swiss mice showed that the (99m)Tc(CO)(3)-HTIDA crosses the blood-brain barrier successfully with a brain uptake of 0.5%ID/g at 5min post injection. The other relevant observations from biodistribution studies included no significant uptake in any other organ and fast clearance from blood, lungs and liver.     

Preparation and comparative evaluation of 99mTc‐HYNIC‐cNGR and 99mTc‐HYNIC‐PEG2‐cNGR as tumor‐targeting molecular imaging probes

The tripeptide sequence asparagine‐glycine‐arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC‐c(NGR) and HYNIC‐PEG₂‐c(NGR), were synthesized, radiolabeled with ^99mTc, and evaluated in CD13‐positive human fibrosarcoma HT‐1080 tumor xenografts. The radiotracers, ^99mTc‐HYNIC‐c(NGR) and ^99mTc‐HYNIC‐PEG₂‐c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being ?2.33 ± 0.05 and ?2.61 ± 0.08. The uptake of 2 radiotracers ^99mTc‐HYNIC‐c(NGR) and ^99mTc‐HYNIC‐PEG₂‐c(NGR) was similar in nude mice bearing human fibrosarcoma HT‐1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of ^99mTc‐labeled HYNIC peptide could not be modulated through introduction of PEG₂ unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention.     

Insight into the PEC and interfacial charge transfer kinetics at the Mo doped BiVO4 photoanodes

BiVO₄ is a promising photoanode material for the photoelectrochemical (PEC) oxidation of water; however, its poor charge transfer, transport, and slow surface catalytic activity limit the expected theoretical efficiency. Herein, we have investigated the effect of Mo doping on SnO₂ buffer layer coated BiVO₄ for PEC water splitting. SnO₂ and Mo doped BiVO₄ layers are coated with layer by layer deposition through a precursor solution based spin coating technique followed by annealing. At 5% doping of Mo, the sample (SBM5) shows a maximum current density of 1.65 mA cm⁻² at 1.64 V vs. RHEl in 0.1 M phosphate buffer solution under AM 1.5 G solar simulator, which is about 154% improvement over the sample without Mo (SBM0). The significant improvement in the photocurrent upon Mo doping is due to the improvement of various bulk and interfacial properties in the materials as measured by UV-vis spectroscopy, electrochemical impedance spectroscopy (EIS), Mott–Schottky analysis, and open-circuit photovoltage (OCPV). The charge transfer kinetics at the BiVO₄/electrolyte interface are investigated to simulate the oxygen evolution process in photoelectrochemical water oxidation in the feedback mode of scanning electrochemical microscopy (SECM) using 2 mM [Fe(CN)₆]³⁻ as the redox couple. SECM investigation reveals a significant improvement in effective hole transfer rate constant from 2.18 cm s⁻¹ to 7.56 cm s⁻¹ for the hole transfer reaction from the valence band of BiVO₄ to [Fe(CN)₆]⁴⁻ to oxidize into [Fe(CN)₆]³⁻ with the Mo doping in BiVO₄. Results suggest that Mo⁶⁺ doping facilitates the hole transfer and suppresses the back reaction. The synergistic effect of fast forward and backward conversion of Mo⁶⁺ to Mo⁵⁺ expected to facilitate the V⁵⁺ to V⁴⁺ which has an important step to improve the photocurrent.

BiVO₄ is a promising photoanode material for the photoelectrochemical (PEC) oxidation of water; however, its poor charge transfer, transport, and slow surface catalytic activity limit the expected theoretical efficiency.     

99mTc carbonyl t-butyl isonitrile: a potential new agent for myocardial perfusion imaging

OBJECTIVE: The recent development of mixed ligand complexes using a 99mTc tricarbonyl synthon has prompted us to revisit the first generation product, 99mTc-t-butyl isonitrile (TBI), for possible myocardial imaging after modification of the 99mTc core to a mixed ligand core of carbonyl and t-butyl isonitrile. The easy availability of TBI from commercial sources and the recent promising development of a 'kit' procedure to prepare the 99mTc tricarbonyl aqua synthon/precursor [99mTc(H2O)3(CO)3]+ were other factors that triggered this work. METHODS: The carbonyl precursor (37-370 MBq/0.5 ml) was synthesized and reacted with TBI (3 mg.ml-1) at room temperature and at pH 8 for 1 h. [99mTc(CO)3(TBI)3]+ was characterized by C18 reverse phase HPLC in gradient mode with water and acetonitrile as solvent. Biodistribution studies were carried out in normal mice and planar images were acquired in rabbit at 5 min, 30 min, 1 h, 2 h and 4 h post-injection to assess heart uptake and soft tissue retention. [99mTc(CO)3(TBI)3]+was formed as a single species in >95% yield and was found to be stable. Biodistribution studies in mice revealed 2.3 (+/-0.2)% uptake in heart at 5 min p.i. with heart/liver, heart/lung and heart/blood ratios of 1.5, 2.0 and 30, respectively. Imaging studies in rabbits showed high uptake in myocardium, with negligible activity in blood and lungs, at 5 min p.i. that washed out of the heart after 4 h. CONCLUSION: [99mTc(CO)3(TBI)3]+ could be prepared in >95% yields. The complex showed high myocardial uptake with desirable rate of washout from heart in rabbits. [99mTc(CO)3(TBI)3]+ has potential to extend to larger animal studies and later for clinical evaluation as a myocardial imaging agent.     

Adsorption and anti-corrosion characteristics of vanillin Schiff bases on mild steel in 1 M HCl: experimental and theoretical study

Herein, two Schiff base derivatives of vanillin and divanillin with 2-picolylamine, namely, 2-methoxy-4-((pyridin-2-ylmethylimino)methyl)phenol (compound A) and 3,3′-dimethoxy-5,5′-bis-((pyridin-2-ylmethylimino)methyl)-[1,1′-biphenyl]-2,2′-diol (compound B), respectively, were synthesized. Additionally, their adsorption characteristics and corrosion inhibition behavior were compared for mild steel in 1 M HCl using electrochemical impedance spectroscopy, potentiodynamic polarization and weight loss methods. Compound B was found to impart a better anti-corrosive effect (around 95% inhibition efficiency at 313 K) than compound A. The inhibitors act as effective mixed-type inhibitors and exhibit Langmuir-type adsorption behaviour. The kinetic–thermodynamic parameters together with the data obtained from density functional theory (DFT) and molecular dynamics (MD) simulations illustrate the mechanism of corrosion and mode of adsorption of both inhibitors on the metal surface. The better corrosion mitigation propensity of the dimeric form of the inhibitor (compound B) over the monomeric form (compound A) was tested experimentally and explained according to the theoretical data.

Two Schiff base derivatives of vanillin and divanillin with 2-picolylamine are synthesized and their anti-corrosive propensity for mild steel in aqueous HCl are compared.     

Preparation and bioevaluation of a Tc-labeled chlorambucil analog as a tumor targeting agent

Chlorambucil belongs to a group of nitrogen mustards which are used for the treatment of variety of cancers. Hence, a chlorambucil derivative has been radiolabeled with [^99mTc(CO)₃(H₂O)₃]⁺ core and its efficacy as a tumor targeting agent has been evaluated. Radiochemical yield of the complex was >98% as observed by HPLC. The in vitro studies in MCF-7 breast cancer cells showed about 30% inhibition of the radiolabeled complex in presence of the cold chlorambucil derivative. Biodistribution studies in Swiss mice bearing fibrosarcoma tumor showed an uptake of 3.2±0.3% ID/g at 3 h.p.i.     

Preparation and preliminary bioevaluation of 99mTc(CO)3-11β-progesterone derivative prepared via click chemistry route

IntroductionProgesterone receptors (PRs) overexpressed in breast cancers serve as potential targets for developing radiotracers for use in nuclear medicine. Hence, suitably derivatized progesterone can be envisaged as a potential vector for targeting overexpression of receptors in breast cancer. In the present article, we report the preparation of a ^99mTc(CO)₃-progesterone triazole using the Cu(I)-catalyzed novel click chemistry route. Preliminary evaluation of the radiolabeled derivative has been carried out in binding studies with MCF 7 cell lines.Methods11-Hydroxyprogesterone has been synthetically derivatized to 11-azidoprogesterone. Subsequently, the cycloaddition reaction between progesterone azide and propargyl glycine was carried out to prepare 1,4-bifunctionalized progesterone triazole analogue. The clicked progesterone triazole derivative was radiolabeled with ^99mTc and characterized by HPLC. The chemical characterization of ^99mTc(CO)₃-progesterone triazole has been carried out by preparing its corresponding rhenium complex using the [NEt₄]₂[Re(CO)₃Br₃] precursor. While in vitro studies were carried out in MCF7 cell lines, in vivo distribution studies were performed in female Swiss mice.ResultsThe radiolabeled complex could be prepared in >95% radiochemical yield as determined by HPLC. In vitro studies of ^99mTc(CO)₃-progesterone complex in MCF7 cell lines overexpressing receptors for breast cancer showed binding up to 30%. In vivo distribution studies in female Swiss mice have shown uterine uptake of 0.41 (0.06) % ID/g at 3 h postinjection (pi) and retention therein till 24 h pi.ConclusionThe present study demonstrates a novel and facile route for preparation of ^99mTc-labeled progesterone complex using click chemistry. This strategy can be further extended towards preparation of radiolabeled complexes of other steroidal derivatives.     

Synthesis,characterization and biological activity of 99mTc‐labeled piperidine analogues targeting sigma receptors

Sigma receptors are expressed in high density in various types of cancer cells including brain tumours and are also involved in various diseases of central nervous system. This makes ligands that bind to these receptors, attractive molecular vectors for targeting radiation to the specific sites with the purpose of imaging and therapy of neurological disorders. We report synthesis of three derivatives of 4‐amino‐N‐benzylpiperidine namely, 4‐dithiocarbamato‐N‐benzylpiperidine, 4‐iminodiacetato‐N‐benzylpiperidine and 4‐(N‐benzylpiperidine)‐pyridin‐2‐ylmethyl‐amino)‐acetic acid and their radiolabeling with technetium‐99m. The in vivo evaluation of these radiolabeled compounds has been carried out in mice, for assessment of their binding affinity with sigma receptors. Of the three complexes, [^99mTcN]‐4‐dithiocarbamato‐N‐benzylpiperidine, [^99mTcN]Pip‐DTC exhibited the most promising characteristics with brain uptake of 0.6% ID/g at 5 min.p.i. that reduced to 0.3% ID/g after 2 h.p.i. Competition experiment carried out with [^99mTcN]Pip‐DTC complex, using (+)‐pentazocine showed its specificity towards sigma receptors, as was found to be evident from reduction in the brain uptake of this complex. Introduction of iminodiacetate and pyridine moieties and subsequent radiolabeling did not result in complexes with significant potential of targeting and binding with sigma receptors. Copyright © 2010 John Wiley & Sons, Ltd.     

Comparative study of copper(II)-curcumin complexes as superoxide dismutase mimics and free radical scavengers

Two stoichiometrically different copper(II) complexes of curcumin (stoichiometry, 1:1 and 1:2 for copper:curcumin), were examined for their superoxide dismutase (SOD) activity, free radical-scavenging ability and antioxidant potential. Both the complexes are soluble in lipids and DMSO. The formation constants of the complexes were determined by voltammetry. EPR spectra of the complexes in DMSO at 77K showed that the 1:2 Cu(II)-curcumin complex is square planar and the 1:1 Cu(II)-curcumin complex is distorted orthorhombic. Cu(II)-curcumin complex (1:1) with larger distortion from square planar structure shows higher SOD activity. These complexes inhibit gamma-radiation induced lipid peroxidation in liposomes and react with DPPH acting as free radical scavengers. One-electron oxidation of the two complexes by radiolytically generated azide radicals in Tx-100 micellar solutions produced phenoxyl radicals, indicating that the phenolic moiety of curcumin in the complexes participates in free radical reactions. Depending on the structure, these two complexes possess different SOD activities, free radical neutralizing abilities and antioxidant potentials. In addition, quantum chemical calculations with density functional theory have been performed to support the experimental observations.