Effect of lipophilicity on biological properties of 109Pd-porphyrin complexes: a preliminary investigation

2012 ◽  
Vol 16 (01) ◽  
pp. 64-71 ◽  
Author(s):  
Sudipta Chakraborty ◽  
Tapas Das ◽  
Haladhar D. Sarma ◽  
Sharmila Banerjee
Keyword(s):  
Specific Activity ◽  
Tumor Therapy ◽  
Preliminary Investigation ◽  
Biological Properties ◽  
Biological Behavior ◽  
High Yield ◽  
Tumor Uptake ◽  
Background Ratio ◽  
Biodistribution Studies ◽  
Pd Complexes

The present study is designed to investigate the effect of lipophilicity of 109Pd-porphyrin complexes on their biological properties which were evaluated in tumor-bearing animal model. The insight obtained could be utilized to develop other radiometalated porphyrin complexes with optimum tumor uptake and tumor to background ratio as potential agents for targeted tumor therapy. 109Pd was produced by thermal neutron bombardment on enriched (in 109Pd) metallic palladium target at a flux of 3 × 1013 n/cm2.s for 3 d. 109Pd complexes of three different porphyrin derivatives, namely, 5,10,15,20-tetrakis[3,4- bis(carboxymethyleneoxy)phenyl]porphyrin(I), 5,10,15,20-tetrakis[3,4-bis(carboethoxymethyleneoxy)phenyl]porphyrin(II) and 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin(III), which differ in their peripheral substituents, were synthesized. The biological behavior of the complexes was studied in Swiss mice bearing fibrosarcoma tumors. 109Pd was produced with a specific activity of ~1.85 GBq/mg (50 mCi/mg) and radionuclidic purity of 100%. All the 109Pd complexes were obtained in high yield (>97%) and they exhibited satisfactory in vitro stability at room temperature. The lipophilicity of the complexes follows the order 109Pd-II ≫ 109Pd-III > 109Pd-I. Biodistribution studies revealed that the most lipophilic 109Pd-II complex exhibited highest initial tumor uptake but poor tumor/liver ratio, while 109Pd-III complex exhibited the best tumor/liver ratio with reasonably good tumor accumulation. The lipophilicity of 109Pd-porphyrin complexes was found to have considerable effect on their biological characteristics and radiometal-porphyrin complexes with optimum tumor uptake and adequately high tumor to background ratio could be synthesized by optimization of the lipophilicity through proper selection of peripheral substituents.

Formulation of ‘ready-to-use’ human clinical doses of 177Lu-labeled bisphosphonate amide of DOTA using moderate specific activity 177Lu and its preliminary evaluation in human patient

2020 ◽  
Vol 108 (8) ◽  
pp. 661-672
Author(s):  
Sudipta Chakraborty ◽  
Priyalata Shetty ◽  
Rubel Chakravarty ◽  
K. V. Vimalnath ◽  
Chandan Kumar ◽  
...  
Keyword(s):  
Specific Activity ◽  
Specific Binding ◽  
Preliminary Investigation ◽  
Skeletal Metastases ◽  
Preliminary Evaluation ◽  
Binding Studies ◽  
Human Patient ◽  
Biodistribution Studies ◽  
Target Organs

AbstractRadiolabeled macrocyclic bisphosphonate ligands have recently been demonstrated to be highly efficacious in treatment of patients with painful bone metastases. Herein, we report a robust protocol for formulation of therapeutically relevant doses of 177Lu-labeled bisphosphonate amide of DOTA (BPAMD) using moderate specific activity 177Lu produced by direct (n,γ) route and its preliminary investigation in human patients. Doses (2.8 ± 0.2 GBq) were formulated with high radiochemical purity (98.3 ± 0.4 %) using a protocol optimized after extensive radiochemical studies. In vitro binding studies with mineralized osteosarcoma cells demonstrated specific binding of the radiotracer. Biodistribution studies in healthy Wistar rats demonstrated rapid skeletal accumulation with fast clearance from the non-target organs. In a patient administered with 555 MBq dose of 177Lu-BPAMD, intense radiotracer uptake was observed in the metastatic skeletal lesions with insignificant uptake in any other major non-targeted organs. Preliminary clinical investigations carried out after administration of 2.6 GBq of 177Lu-BPAMD revealed significant reduction in pain after 1 week without any adverse effects. The developed protocol for formulation of 177Lu-BPAMD doses using moderate specific activity carrier added 177Lu has been found to be effective and warrants wider investigations in patients with painful skeletal metastases.

scholarly journals Clickable Radiocomplexes With Trivalent Radiometals for Cancer Theranostics: In vitro and in vivo Studies

2021 ◽  
Vol 8 ◽  
Author(s):  
Alice D'Onofrio ◽  
Francisco Silva ◽  
Lurdes Gano ◽  
Urszula Karczmarczyk ◽  
Renata Mikołajczak ◽  
...  
Keyword(s):  
Specific Activity ◽  
Ex Vivo ◽  
High Specific Activity ◽  
In Vivo Studies ◽  
Tumor Uptake ◽  
Biodistribution Studies ◽  
Radiochemical Yields ◽  
Analysis Of The Images

Pre-targeting approaches based on the inverse-electron-demand Diels-Alder (iEDDA) reaction between strained trans-cyclooctenes (TCO) and electron-deficient tetrazines (Tz) have emerged in recent years as valid alternatives to classic targeted strategies to improve the diagnostic and therapeutic properties of radioactive probes. To explore these pre-targeting strategies based on in vivo click chemistry, a small family of clickable chelators was synthesized and radiolabelled with medically relevant trivalent radiometals. The structure of the clickable chelators was diversified to modulate the pharmacokinetics of the resulting [111In]In-radiocomplexes, as assessed upon injection in healthy mice. The derivative DOTA-Tz was chosen to pursue the studies upon radiolabelling with 90Y, yielding a radiocomplex with high specific activity, high radiochemical yields and suitable in vitro stability. The [90Y]Y-DOTA-Tz complex was evaluated in a prostate cancer PC3 xenograft by ex-vivo biodistribution studies and Cerenkov luminescence imaging (CLI). The results highlighted a quick elimination through the renal system and no relevant accumulation in non-target organs or non-specific tumor uptake. Furthermore, a clickable bombesin antagonist was injected in PC3 tumor-bearing mice followed by the radiocomplex [90Y]Y-DOTA-Tz, and the mice imaged by CLI at different post-injection times (p.i.). Analysis of the images 15 min and 1 h p.i. pointed out an encouraging quick tumor uptake with a fast washout, providing a preliminary proof of concept of the usefulness of the designed clickable complexes for pre-targeting strategies. To the best of our knowledge, the use of peptide antagonists for this purpose was not explored before. Further investigations are needed to optimize the pre-targeting approach based on this type of biomolecules and evaluate its eventual advantages.

scholarly journals Biological behavior of a new 68Ga-labelled glucose derivative as a potential agent for tumor imaging

2021 ◽  
Vol 2058 (1) ◽  
pp. 012037
Author(s):  
V K Tishchenko ◽  
V M Petriev ◽  
K A Kuzenkova ◽  
I N Zavestovskaya ◽  
P V Shegai ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Biological Behavior ◽  
Tumor Uptake ◽  
Aseptic Inflammation ◽  
Promising Alternative ◽  
Tumor Bearing ◽  
Pet Tracer ◽  
Biodistribution Studies ◽  
Positron Emitter ◽  
Glucose Derivative

Abstract Glucose analogs and derivatives labeled with positron emitter 68Ga are considered to be a promising alternative to widely used radiotracer 18F-FDG for tumor PET imaging. In this study a biodistribution of a new glucose derivative labeled with 68Ga (68Ga-NODA-thioglucose) was investigated. All biodistribution studies were carried out in Balb/c mice with experimental model of tumor or aseptic inflammation. The tumor uptake of 68Ga-NODA-TG decreased throughout the study from 3.00±0.08 % ID/g to 1.06±0.04 %ID/g. The peak amount of 68Ga-NODA-TG in muscle with inflammation reached 4.33±0.12 % ID/g, decreasing to 0.23±0.08 % ID/g. In other organs and tissues the biodistribution of 68Ga-NODA-TG was similar in tumor-bearing mice and mice with aseptic inflammation. In conclusion, the obtained results suggest that 68Ga-NODA-TG has the potential for clinical application as a PET tracer.

BOTANICAL COMPOSITION AND PRODUCTIVITY OF PERENNIAL GRASSES AGROPHYTOCENOSES WITH TETRAPLOID MEADOW CLOVER

1970 ◽  
pp. 59-62
Author(s):  
N. I. Kasatkina ◽  
Zh. S. Nelyubina
Keyword(s):  
Dry Weight ◽  
Single Species ◽  
Lotus Corniculatus ◽  
Specific Weight ◽  
Biological Properties ◽  
Phleum Pratense ◽  
Perennial Grasses ◽  
High Yield ◽  
Botanical Composition ◽  
The Third

The biological properties of plants, their mutual relations under different growth conditions and at different periods of their life, must be known for obtaining highly productive agrophytocenoses with participation of a meadow clover (Trifolium pratense L.). Botanical composition and fodder productivity of perennial grasses in agrocenoses with participation of meadow tetraploid clover Kudesnik were studied in 2014-2017. It was revealed that in the first and second years of use the agrophytocenosis, the yield of green mass was formed due to meadow tetraploid clover, the share of its participation in the first mowing was at level of 71-87% and 64-97% respectively. Specific weight of clover in multispecies agrocenoses considerably decreased by the third year of use: in the first mowing up to 32-68%, in the second - up to 8-52%. At the same time, the percentage of long-term herbaceous grasses increased: meadow timothy (Phleum pratense L.) - up to 34-54%, eastern galega (Galéga orientális Lam.) - up to 33%, changeable alfalfa (Medicago x varia Martyn) - up to 22-54%, lotus corniculatus (Lotus corniculatus L.) - up to 14-19%. The proportion of weed admixture in single-species clover planting was 12%, in agrocenoses - 2-14%. The grass mixtures clover + timothy and clover + alfalfa + timothy were less infested by weeds. High yield of dry weight of single-species sowing of meadow tetraploid clover was obtained in the first two years of use - 7.8 and 6.5 tons / ha, respectively. By the third year of use, the productivity of clover has decreased to 2.9 t / ha. On average, for three years of use, the highest yield (6.2-6.3 t / ha) was formed by agrocenoses meadow tetraploid clover + meadow timothy and meadow tetraploid clover + changeable alfalfa + meadow timothy.

scholarly journals Whole cell-based catalyst for enzymatic production of the osmolyte 2-O-α-glucosylglycerol

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Katharina N. Schwaiger ◽  
Monika Cserjan-Puschmann ◽  
Gerald Striedner ◽  
Bernd Nidetzky
Keyword(s):  
Specific Activity ◽  
Dry Mass ◽  
High Yield ◽  
Sucrose Phosphorylase ◽  
Bifidobacterium Adolescentis ◽  
Enzymatic Production ◽  
Intracellular Enzyme ◽  
Whole Cell ◽  
Freeze Thaw ◽  
Thaw Cycle

Abstract Background Glucosylglycerol (2-O-α-d-glucosyl-sn-glycerol; GG) is a natural osmolyte from bacteria and plants. It has promising applications as cosmetic and food-and-feed ingredient. Due to its natural scarcity, GG must be prepared through dedicated synthesis, and an industrial bioprocess for GG production has been implemented. This process uses sucrose phosphorylase (SucP)-catalyzed glycosylation of glycerol from sucrose, applying the isolated enzyme in immobilized form. A whole cell-based enzyme formulation might constitute an advanced catalyst for GG production. Here, recombinant production in Escherichia coli BL21(DE3) was compared systematically for the SucPs from Leuconostoc mesenteroides (LmSucP) and Bifidobacterium adolescentis (BaSucP) with the purpose of whole cell catalyst development. Results Expression from pQE30 and pET21 plasmids in E. coli BL21(DE3) gave recombinant protein at 40–50% share of total intracellular protein, with the monomeric LmSucP mostly soluble (≥ 80%) and the homodimeric BaSucP more prominently insoluble (~ 40%). The cell lysate specific activity of LmSucP was 2.8-fold (pET21; 70 ± 24 U/mg; N = 5) and 1.4-fold (pQE30; 54 ± 9 U/mg, N = 5) higher than that of BaSucP. Synthesis reactions revealed LmSucP was more regio-selective for glycerol glycosylation (~ 88%; position O2 compared to O1) than BaSucP (~ 66%), thus identifying LmSucP as the enzyme of choice for GG production. Fed-batch bioreactor cultivations at controlled low specific growth rate (µ = 0.05 h−1; 28 °C) for LmSucP production (pET21) yielded ~ 40 g cell dry mass (CDM)/L with an activity of 2.0 × 104 U/g CDM, corresponding to 39 U/mg protein. The same production from the pQE30 plasmid gave a lower yield of 6.5 × 103 U/g CDM, equivalent to 13 U/mg. A single freeze–thaw cycle exposed ~ 70% of the intracellular enzyme activity for GG production (~ 65 g/L, ~ 90% yield from sucrose), without releasing it from the cells during the reaction. Conclusions Compared to BaSucP, LmSucP is preferred for regio-selective GG production. Expression from pET21 and pQE30 plasmids enables high-yield bioreactor production of the enzyme as a whole cell catalyst. The freeze–thaw treated cells represent a highly active, solid formulation of the LmSucP for practical synthesis.

In silico and in vivo study of radio-iodinated nefiracetam as a radiotracer for brain imaging in mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
M. H. Sanad ◽  
A. B. Farag ◽  
S. F. A. Rizvi
Keyword(s):  
Brain Imaging ◽  
Radiochemical Purity ◽  
High Yield ◽  
High Uptake ◽  
Oxidizing Agent ◽  
Receptor Ligand ◽  
Nootropic Agent ◽  
Biodistribution Studies

Abstract This study presents development and characterization of a radiotracer, [125I]iodonefiracetam ([125I]iodoNEF). Labeling with high yield and radiochemical purity was achieved through the formation of a [125I]iodoNEF radiotracer after investigating many factors like oxidizing agent content (chloramines-T (Ch-T)), substrate amount (Nefiracetam (NEF)), pH of reaction mixture, reaction time and temperature. Nefiracetam (NEF) is known as nootropic agent, acting as N-methyl-d-aspartic acid receptor ligand (NMDA). The radiolabeled compound was stable, and exhibited the logarithm of the partition coefficient (log p) value of [125I]iodonefiracetam as 1.85 (lipophilic). Biodistribution studies in normal mice confirmed the suitability of the [125I]iodoNEF radiotracer as a novel tracer for brain imaging. High uptake of 8.61 ± 0.14 percent injected dose/g organ was observed in mice

scholarly journals Development, Validation and Application of a UHPLC-MS Method for the Quantification of Chios Mastic Gum Triterpenoids in Human Plasma

Planta Medica ◽  
2021 ◽  
Author(s):  
Vincent Brieudes ◽  
Eleni V. Mikropoulou ◽  
Errikos Kallergis ◽  
Andriana C. Kaliora ◽  
Efstathia Papada ◽  
...  
Keyword(s):  
Human Plasma ◽  
Biological Fluids ◽  
Structural Characteristics ◽  
Biological Properties ◽  
Lipid Lowering ◽  
High Yield ◽  
Limit Of Quantification ◽  
Isolation And Characterization ◽  
Starting Point ◽  
Chios Mastic Gum

AbstractChios mastic gum is the resinous secretion obtained from the barks of the shrub Pistacia lentiscus var. Chia, which is endemic to the Greek island of Chios. Since antiquity, Chios mastic gum has found several uses as a phytotherapeutic remedy, primarily for the treatment of gastrointestinal disorders while recently, Chios mastic gum was also recognized by EMA as an herbal medicinal product with specific indications. Chios mastic gumʼs biological properties are attributed to triterpenes which comprise the major chemical group (approx. 70%) and notably isomasticadienonic acid and masticadienonic acid. However, due to their structural characteristics, the isolation thereof in high yield and purity is challenging and since they are not commercially available, pharmacological studies aiming to assess their biological properties are limited. In the present work, masticʼs phytochemical investigation by UPLC-HRMS is followed by the isolation and characterization of isomasticadienonic acid and masticadienonic acid to be used as analytical standards for their accurate and reliable quantification in human plasma. A UHPLC-tQ-MS method that was developed and validated (in terms of specificity, linearity, limit of quantification, accuracy and precision), for the direct quantification of the targeted compounds in the low ng/mL range of concentration, was subsequently implemented on plasma samples of healthy volunteers thus demonstrating its fitness for purpose. The results presented herein might provide insight to the understanding of this traditional natural product consumed notably for its anti-inflammatory, antioxidant and lipid lowering properties. Moreover, this method might serve as a starting point for any study aiming to monitor bioactive triterpenes in biological fluids.

scholarly journals Milestones in research on tobacco mosaic virus

1999 ◽  
Vol 354 (1383) ◽  
pp. 521-529 ◽  
Author(s):  
B. D. Harrison ◽  
T. M. A. Wilson
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Virus Resistance ◽  
Dominant Role ◽  
Biological Properties ◽  
Mosaic Disease ◽  
Genetically Engineered ◽  
High Yield ◽  
Past Century ◽  
Avirulence Genes

Beijerinck's (1898) recognition that the cause of tobacco mosaic disease was a novel kind of pathogen became the breakthrough which led eventually to the establishment of virology as a science. Research on this agent, tobacco mosaic virus (TMV), has continued to be at the forefront of virology for the past century. After an initial phase, in which numerous biological properties of TMV were discovered, its particles were the first shown to consist of RNA and protein, and X–ray diffraction analysis of their structure was the first of a helical nucleoprotein. In the molecular biological phase of research, TMV RNA was the first plant virus genome to be sequenced completely, its genes were found to be expressed by cotranslational particle disassembly and the use of subgenomic mRNA, and the mechanism of assembly of progeny particles from their separate parts was discovered. Molecular genetical and cell biological techniques were then used to clarify the roles and modes of action of the TMV non–structural proteins: the 126 kDa and 183 kDa replicase components and the 30 kDa cell–to–cell movement protein. Three different TMV genes were found to act as avirulence genes, eliciting hypersensitive responses controlled by specific, but different, plant genes. One of these (the N gene) was the first plant gene controlling virus resistance to be isolated and sequenced. In the biotechnological sphere, TMV has found several applications: as the first source of transgene sequences conferring virus resistance, in vaccines consisting of TMV particles genetically engineered to carry foreign epitopes, and in systems for expressing foreign genes. TMV owes much of its popularity as a research model to the great stability and high yield of its particles. Although modern methods have much decreased the need for such properties, and TMV may have a less dominant role in the future, it continues to occupy a prominent position in both fundamental and applied research.

Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification

Development ◽  
1992 ◽  
Vol 114 (3) ◽  
pp. 711-720 ◽  
Author(s):  
H.V. Isaacs ◽  
D. Tannahill ◽  
J.M. Slack
Keyword(s):  
Specific Activity ◽  
Biological Properties ◽  
The Body ◽  
Mesoderm Induction ◽  
Gastrula Stage ◽  
Blastula Stage ◽  
Mesoderm Formation ◽  
Low Levels

We have cloned and sequenced a new member of the fibroblast growth factor family from Xenopus laevis embryo cDNA. It is most closely related to both mammalian kFGF (FGF-4) and FGF-6 but as it is not clear whether it is a true homologue of either of these genes we provisionally refer to it as XeFGF (Xenopus embryonic FGF). Two sequences were obtained, differing by 11% in derived amino acid sequence, which probably represent pseudotetraploid variants. Both the sequence and the behaviour of in vitro translated protein indicates that, unlike bFGF (FGF-2), XeFGF is a secreted molecule. Recombinant XeFGF protein has mesoderm-inducing activity with a specific activity similar to bFGF. XeFGF mRNA is expressed maternally and zygotically with a peak during the gastrula stage. Both probe protection and in situ hybridization showed that the zygotic expression is concentrated in the posterior of the body axis and later in the tailbud. Later domains of expression were found near the midbrain/hindbrain boundary and at low levels in the myotomes. Because of its biological properties and expression pattern, XeFGF is a good candidate for an inducing factor with possible roles both in mesoderm induction at the blastula stage and in the formation of the anteroposterior axis at the gastrula stage.

scholarly journals Preparation of crotalus venom radiolabeled with technetium-99m as a tool for biodistribution study

2005 ◽  
Vol 48 (spe2) ◽  
pp. 9-12 ◽  
Author(s):  
Priscilla Brunelli Pujatti ◽  
Carlos Jorge Rodrigues Simal ◽  
Raquel Gouvêa dos Santos
Keyword(s):  
Biological Activity ◽  
High Efficiency ◽  
High Yield ◽  
Clinical Use ◽  
Crude Venom ◽  
Technetium 99M ◽  
Biodistribution Studies ◽  
Nuclear Medicine Procedures ◽  
Distribution Studies ◽  
Exogenous Source

Technetium-99m (99mTc) has been the radionuclide of choice for nuclear medicine procedures and experimental research. Because of its optimal nuclear properties, 99mTc is suitable for high efficiency detection with the advantage of reduced radiological waste. Crotalus venom (CV) has been shown to reduce tumors in clinical studies and tissue distribution studies are very important for clinical use. The goal of this work was to obtain CV labeled with 99mTc which preserves its biological activity. After labeling, biological activity was assessed by hemolytic activity evaluation. Labeled and crude venom caused indirect hemolysis provided that the incubation medium contained an exogenous source of lecithin. High yield radiolabeled-CV was obtained and biological activity was preserved. The results suggest that 99mTc-CV can be a useful tool for biodistribution studies.

Sign in / Sign up

Export Citation Format

Share Document