Peptide derived from plant defensins: A promising Ga radiolabelled agent for diagnostic of infection foci in PET.

The development of new radiopharmaceuticals for the detection of hidden infection foci has great relevance for early detection and the selection of the correct treatment, particularly in immunosuppressed patients. In that sense, the labelling of antimicrobial peptides (AMPs) that are capable of binding specifically to the pathogenic microorganism which causes the infection, should provide a sufficiently specific agent, able to distinguish an infection from a sterile inflammation. Defensins are particularly interesting molecules with antimicrobial activity, the EcgDf1 defensin was identified from the genome of a Uruguayan native plant, Erythrina crista-galli, the 'Ceibo' tree.

Prenylated Flavanone Isolated from Dalea Species as a Potential Multitarget-Neuroprotector in an In Vitro Alzheimer's Disease Mice Model.

Alzheimer's disease (AD) involves a neurodegenerative process that has not yet been prevented, reversed, or stopped. Continuing with the search for natural pharmacological treatments, flavonoids are a family of compounds with proven neuroprotective effects and multi-targeting behavior. The American genus Dalea L.

Synthesis of a [F]F Estradiol Derivative via Click Chemistry Using an Automated Synthesis Module: In Vitro Evaluation as Potential Radiopharmaceutical for Breast Cancer Imaging.

"Click reactions" are a very useful tool for the selective conjugation of different molecular subunits to produce complex structures in a simple way. In this paper, we present the application of Cu(I)-catalyzed biorthogonal reactions between alkynes and azides to the indirect radiofluorination of an estradiol derivative with potential applications in estrogen receptor imaging. The procedure was fully developed on an automated synthesis platform, and conditions were optimized to achieve the desired product with a reasonable yield without precipitation.

Development and Evaluation of Tc Tricarbonyl Complexes Derived from Flutamide with Affinity for Androgen Receptor.

With the objective to develop a potential Tc radiopharmaceutical for imaging the androgen receptor (AR) in prostate cancer, four ligands bearing the same pharmacophore derived from the AR antagonist flutamide were prepared, labeled with Tc, and their structures corroborated via comparison with the corresponding stable rhenium analogs. All complexes were obtained with high radiochemical purity. Three of the complexes were highly stable, and, due to their favorable physicochemical properties, were further evaluated using AR-positive and AR-negative cells in culture.

Radiosynthesis and validation of [ F]fluoroestradiol in a Synthra plus research platform for use in routine clinical practice.

In this practitioner protocol, the optimization of the radiochemical synthesis of [ F]fluoroestradiol (FES) on the Synthra RNplus research automated platform is described in detail and a quality control (QC) summary of three validation productions is presented. In comparison with published synthesis methods developed on other platforms, the yield was considerably improved (40%-45% ndc). The other important improvement is the reduction of the required concentration of H SO avoiding the production of high concentrations of acidic vapors that can deteriorate the module.

Glycogen Synthase Kinase-3 Maleimide Inhibitors As Potential PET-Tracers for Imaging Alzheimer's Disease: C-Synthesis and Proof of Concept.

Herein we present the evaluation of C-labeled-maleimides as radiotracers for positron emission tomography imaging of GSK-3 associated with Alzheimer's disease (AD). 3-Acetyl-4-(1-[C]-methyl-1-indol-3-yl)[1]pyrrole-2,5-dione ([C]-) was obtained by direct methylation using [C]-CHI and CsCO in DMF with a 31 ± 4% radiochemical yield and a radiochemical purity of 97.7 ± 0.

Development and evaluation of a Tc(V)-nitrido complex derived from estradiol for breast cancer imaging.

Estrogen receptors are overexpressed in 70% of breast cancer and identification of their presence is important to select the appropriate treatment. This work proposes the preparation and evaluation of an estradiol derived as potential ER imaging agent. Ethinylestradiol was derivatized to introduce a dithiocarbamate function for Tc coordination.

Synthesis of an AlF radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform.

Background: Overexpression of prostatic membrane antigen (PSMA) is associated with the progression and prognosis of prostate cancer. There are numerous studies using this peptide with the Ga radionuclide. Previous methods to synthetize F-labeled PSMA ligands with complexes [F]AlF have been achieved.

Development and characterization of a Tc-tricarbonyl-labelled estradiol derivative obtained by "Click Chemistry" with potential application in estrogen receptors imaging.

Assessment of the presence of estrogen receptors in breast cancer is crucial for treatment planning. With the objective to develop a potential agent for estrogen receptors imaging, we present the development and characterization of a Tc-tricarbonyl-labelled estradiol derivative. Using ethinylestradiol as starting material, an estradiol derivative bearing a 1,4-disubstituted 1,2,3-triazole-containing tridentate ligand system was synthesized by "Click Chemistry" and fully characterized.

3-(Benzyloxy)-1-(5-[F]fluoropentyl)-5-nitro-1H-indazole: a PET radiotracer to measure acetylcholinesterase in brain.

Aim: Noninvasive studies of the acetylcholinesterase (AChE) level in Alzheimer's disease (AD) patients can contribute to a better understanding of the disease and its therapeutic. We propose 3-(benzyloxy)-1-(5-[F]fluoropentyl)-5-nitro-1H-indazole, [F]-IND1, structurally related to the AChE-inhibitor CP126,998, as a new positron emission tomography-radiotracer.

Experimental: Radiosynthesis, with 18F, stability, lipophilicity and protein binding of [18F]-IND1 were studied.

Design and development of (99m)tc-'4+1'-labeled dextran-mannose derivatives as potential radiopharmaceuticals for sentinel lymph node detection.

The synthesis, labeling, and biological evaluation of a dextran derivative (DCM-30-iso) as potential radiopharmaceutical for sentinel lymph node imaging is presented. DCM-30-iso bears mannose as active moiety and isocyanide as ligand for technetium through the formation of a '4+1' Tc(III) mixed-ligand complex. A second derivative without mannose (DC-25-iso) was also prepared and evaluated as control.

Synthesis, in vitro and in vivo characterization of two novel 68Ga-labelled 5-nitroimidazole derivatives as potential agents for imaging hypoxia.

Introduction: Hypoxia imaging is an important field in radiopharmaceutical research since hypoxic cells are very resistant to radiation treatment and diffusional limitations restrict the efficacy of chemotherapy. Gallium-68 is a widely used radionuclide for positron emission tomography (PET) due to the availability of the (68)Ge/(68)Ga-generator. With the aim to develop new potential [(68)Ga]-radiopharmaceuticals for imaging hypoxia, we have synthesized and evaluated two novel (68)Ga-labelled 5-nitroimidazole derivatives.

Influence of ligand denticity on the properties of novel ⁹⁹mTc(I)-carbonyl complexes. Application to the development of radiopharmaceuticals for imaging hypoxic tissue.

An important issue in the development of metal-based radiopharmaceuticals is the selection of the labelling strategy in order to couple the metal to the pharmacophore without losing the biological activity. With the aim to evaluate the correlation between ligand denticity and biological behaviour of the corresponding (99m)Tc complexes, we designed a tridentate and a bidentate 5-nitroimidazole derivatives suitable for (99m)Tc(I) tricarbonyl complexation and with potential use as radiopharmaceuticals towards hypoxic tissue diagnosis. Ligands were synthesized using metronidazol, a pharmaceutical containing the bioreductive pharmacophore as starting material.

Synthesis, in vitro and in vivo characterization of novel 99mTc-'4+1'-labeled 5-nitroimidazole derivatives as potential agents for imaging hypoxia.

Unlabelled: The evaluation of oxygenation status of solid tumors is an important field of radiopharmaceutical research. With the aim to develop new potential 99mTc-radiopharmaceuticals for imaging hypoxia, we have synthesized two novel isocyanide derivatives of metronidazole, which has demonstrated high affinity for hypoxic tumors in vitro and in vivo.

Methods: Metronidazole derivatives 4-isocyano-N-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]butanamide (M1) and 1-(4-isocyanobutanoyl)-4-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]piperazine (M2) were synthesized, and labeling was performed through preparation of their corresponding 99mTc-(4+1) complexes, 99mTc-NS3M1 and 99mTc-NS3M2.

Synthesis and biological characterisation of novel dithiocarbamate containing 5-nitroimidazole (99m)Tc-complexes as potential agents for targeting hypoxia.

With the aim to develop new potential (99m)Tc-radiopharmaceuticals for imaging hypoxia based on the formation of Tc-nitrido complexes, two novel dithiocarbamate containing metronidazole derivatives (L1 and L2) have been prepared and characterised. The synthesis of L1 and L2 was achieved in excellent yield and high purity. Labelling with (99m)Tc was successfully performed using a low ligand concentration (approximately 2-3mg) and the desired products were obtained with high radiochemical purity (>90%).

Flow-injection determination of phenylephrine hydrochloride in pharmaceutical dosage forms with on-line solid-phase extraction and spectrophotometric detection.

A flow injection method is proposed for the determination of phenylephrine hydrochloride in pharmaceutical dosage forms. The method involves the use of on-line solid-phase extraction by means of a microcolumn containing Dowex 50W X8 ion-exchange resin for the separation of the analyte prior to colour development and spectrophotometric detection in the visible region. The influence of preconcentration flow, preconcentration pH and elution volume was studied.

Preparation and characterization of technetium and rhenium tricarbonyl complexes bearing the 4-nitrobenzyl moiety as potential bioreductive diagnostic radiopharmaceuticals. In vitro and in vivo studies.

The synthesis of a ligand containing a nitrobenzyl group as bioreductive pharmacophore and the preparation of the corresponding technetium and rhenium complexes are presented. (99m)Tc labelling was performed in high yield (>90%) by ligand substitution using fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) as precursor. The structure of the technetium complex was established by chromatographic comparison with the analogous rhenium compound which was fully characterized by elemental analysis, spectroscopic methods and X-ray crystallography.

Synthesis and characterization of thiol containing furoxan derivatives as coligands for the preparation of potential bioreductive radiopharmaceuticals.

The synthesis and characterization of thiol-containing 1,2,5-oxadiazole N-oxide (TONO) derivatives and their use as monodentate coligands for the preparation of (99m)Tc complexes is presented. 3-Mercaptomethyl-4-phenyl-1,2,5-oxadiazol N(2)-oxide and 3-(4-mercaptophenylmethylidenhydrazinocarbonyloxymethyl)-4-phenyl-1,2,5-oxadiazol N(2)-oxide were successfully synthesized and combined with the tridentate ligand N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA) to prepare "3+1 mixed ligand" technetium complexes. The( 99m)Tc complexes were obtained in high yield and radiochemical purity using low concentration of ligand and coligand.

Flow-injection spectrophotometric determination of paracetamol in tablets and oral solutions.

A flow injection method is proposed for the determination of paracetamol in pharmaceutical dosage forms. The method is based on the nitration of paracetamol with sodium nitrite, and the absorption of the reaction product is measured at 430 nm in alkaline medium. Unlike other colorimetric methods used for determination of paracetamol, this method does not require the use of heat.