A5039151422- Radiopharmaceutical Chemistry and Applications
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Medical Imaging Techniques and Applications
- Amino Acid Enzymes and Metabolism
- Epigenetics and DNA Methylation
- Medical Imaging and Pathology Studies
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Orthopedic Infections and Treatments
- Synthesis and Biological Evaluation
- Lanthanide and Transition Metal Complexes
- Metal complexes synthesis and properties
- Chemical Synthesis and Analysis
- Orthopaedic implants and arthroplasty
- Chemical Reactions and Isotopes
- Cell Adhesion Molecules Research
- Fluorine in Organic Chemistry
- Click Chemistry and Applications
- Atherosclerosis and Cardiovascular Diseases
- Protease and Inhibitor Mechanisms
- Metabolism and Genetic Disorders
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
Institute of Nuclear & Radiological Sciences and Technology, Energy & Safety
2021-2024
National Centre of Scientific Research "Demokritos"
2006-2024
ETH Zurich
2013-2019
Queen's Medical Centre
2019
University of Nottingham
2019
Charles Humbert 8
2016
École Polytechnique Fédérale de Lausanne
2014
National and Kapodistrian University of Athens
2008
Aristotle University of Thessaloniki
2006
Most chemical techniques used to produce antibody-drug conjugates (ADCs) result in a heterogeneous mixture of species with variable drug-to-antibody ratios (DAR) which will potentially display different pharmacokinetics, stability, and safety profiles. Here we investigated two strategies obtain homogeneous ADCs based on site-specific modification deglycosylated antibodies by microbial transglutaminase (MTGase), forms isopeptidic bonds between Gln Lys residues. We have previously shown that...
Antibody–drug conjugates (ADCs) have demonstrated clinical benefits that led to the recent FDA approval of KADCYLA and ADCETRIS. Most ADCs are currently in use or development, including ADCETRIS, produced by chemical conjugation a toxin via either lysine cysteine residues, inevitably leading heterogeneous products with variable drug-to-antibody ratios (DARs). Here, we describe vitro vivo characterization four novel based on anti-CD30 antibody cAC10, which has same polypeptide backbone as...
Research towards the non-invasive imaging of atherosclerotic plaques is high clinical priority as early recognition vulnerable may reduce incidence cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed inflammation-induced protease involved in process plaque vulnerability. In this study, FAP mRNA and levels were investigated by quantitative polymerase chain reaction immunohistochemistry, respectively, human endarterectomized carotid plaques. A published...
We report a novel prosthetic group based on heterocyclic methylsulfone derivative for the rapid, stable, and chemoselective (18)F-labeling of thiol-containing (bio)molecules under mild aqueous reaction conditions. Compared to established maleimide approaches, new methodology displays some clear advantages imaging probe development.
Hepatitis B virus (HBV) remains a global health threat. Ribonuclease H (RNase H), part of the polymerase protein, cleaves pgRNA template during viral genome replication. Inhibition RNase activity prevents (+) DNA strand synthesis and results in accumulation non-functional genomes, terminating replication cycle. H, though promising, an under-explored drug target against HBV. We previously reported identification series N-hydroxypyridinedione (HPD) imines that effectively inhibit HBV H. In our...
The quinazoline derivatives (3-chloro-4-fluorophenyl)quinazoline-4,6-diamine (2) and (3-bromophenyl)quinazoline-4,6-diamine (3) were labelled with 99mTc using the "4 + 1" mixed-ligand system [Tc(NS3)(CN-R)] tricarbonyl moiety fac-[Tc(CO)3]+. In approach technetium(III) is stabilized by a monodentate isocyanide bearing fragment (L11, L22) tetradentate tripodal ligand tris(2-mercaptoethyl)-amine (NS3). approach, 99mTc-labelling was performed in two-step procedure, complexes [Tc(NS3)(L11)] (7a)...
As a continuation of our research efforts toward the development tryptophan-based radiotracers for tumor imaging with positron emission tomography (PET), three new fluoroethoxy tryptophan analogues were synthesized and evaluated in vivo. These tracers (namely, 4-(2-[18F]fluoroethoxy)-dl-tryptophan ([18F]4-FEHTP), 6-(2-[18F]fluoroethoxy)-dl-tryptophan ([18F]6-FEHTP), 7-(2-[18F]fluoroethoxy)-dl-tryptophan ([18F]7-FEHTP) carry side chain either at positions 4-, 6-, or 7- indole core. Reference...
Aiming at developing mechanism-based amino acid (18)F-PET tracers for tumor imaging, we synthesized two (18)F-labeled analogues of 5-hydroxy-l-[β-(11)C]tryptophan ([(11)C]5HTP) whose excellent in vivo performance neuroendocrine tumors is mainly attributed to its decarboxylation by aromatic decarboxylase (AADC), an enzyme overexpressed these malignancies. Reference compounds and precursors were following multistep synthetic approaches. Radiosynthesis was accomplished good radiochemical yields...
Fibroblast growth factor 21 (FGF21) has been shown to rapidly lower body weight in the Siberian hamster, a preclinical model of adiposity. This induced negative energy balance mediated by FGF21 is associated with both lowered caloric intake and increased expenditure. Previous research demonstrated that adipose tissue (AT) one primary sites action may be responsible for its ability increase whole-body metabolic rate. The present study sought determine relative importance white (subcutaneous...
A new prosthetic group is reported for 18F-labelling of peptides and proteins based on the chemoselective ligation potassium acyltrifluoroborates (KATs) hydroxylamines without any detectable 18F/19F isotope exchange at acyltrifluoroborate moiety. The building block appended via a common amide bond room temperature with no need protecting groups which enables an effective orthogonal 18F-radiolabelling.
The synthesis and characterization of three neutral tricarbonyl fac-M(CO)3(NNO) (M = Re, 99mTc) complexes based on the picolylamine N,N-diacetic acid (PADA) ligand is reported. One two carboxylate groups PADA efficiently conveniently derivatized with an amine nucleophile through use anhydride. In this work, aniline, benzylamine pyrrolidine were used as model nucleophiles. rhenium synthesized using [NEt4]2[Re(CO)3Br3] precursor fully characterized by elemental analysis, spectroscopic methods,...
Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) L(+)-cysteine bearing donor atom set NNO SNO, respectively. The rhenium precursors ReBr(CO)5 fac-[NEt4]2[ReBr3(CO)3] were used for preparation of Re complexes fac-[Re(NNO)(CO)3] (5a) fac-[Re(SNO)(CO)3] (7a) which characterized by NMR IR...
The costimulatory molecule CD80 is an early marker for immune activation. It upregulated on activated antigen-presenting cells. We aimed at developing a tracer imaging by positron emission tomography (PET). Novel ligands were synthesized and tested SPR affinity to human (hCD80) displacement of endogenous ligands. Several compounds bound with one-digit nanomolar hCD80 displaced CTLA-4 CD28 concentrations. A structure–affinity relationship study revealed relevant moieties strong positions...
Radiolabeled gold nanoparticles (AuNPs) have been widely used for cancer diagnosis and therapy over recent decades. In this study, we focused on the development in vitro evaluation of four new Au nanoconjugates radiolabeled with technetium-99m (99mTc) via thiol-bearing ligands attached to NP surface. More specifically, AuNPs two different sizes (2 nm 20 nm, referred as Au(2) Au(20), respectively) were functionalized bifunctional thiol (referred L1H L2H). The shape, size, morphology both bare...
Abstract In this work we report the synthesis, characterization and biological evaluation of two new neutral tricarbonyl fac -M(CO) 3 (NNO) (M=Re, 99m Tc) derivatives WAY-100635 as potential Tc agents for in vivo imaging 5HT 1A receptors. The pharmacophore NNO ligands are based on picolylamine N , -diacetic acid (PADA) ligand their synthesis was achieved through PADA anhydride, showing thus applicability synthetic approach, developed our laboratory, incorporation bioactive amines molecule...
The fac-[M(CO)3(PyA)(P)] and cis-trans-[M(CO)2(PyA)(P)2] neutral complexes (M is Re or 99mTc), based on the mixed ligand strategy with pyrazine-2-carboxylic acid (PyAH) as bidentate N,O triphenylphosphine monodentate P ligand, are presented. Through employment of anhydride pyrazine-2,3-dicarboxylic (PyDA), PyAH scaffold was conveniently derivatized model bioactive amine 1-(2-methoxyphenyl)piperazine, active part 5-HT1A antagonist WAY100635. Reaction either pharmacophore-bearing (L1H)...
The present paper deals with the synthesis and structural characterization of novel neutral oxorhenium(V) complexes general formula ReO[SNO][NN]. simultaneous action tridentate SNO ligand, N-(2-mercaptoacetyl)glycine (1), bidentate NN N-phenylpyridine-2-aldimine (2), on ReOCl3(PPh3)2 leads to formation two isomers 4a 4b ReO[SNO][NN], as a result different orientations ligand. In both cases, donor atoms ligand occupy three positions in equatorial plane distorted octahedron, whereas oxo group...
Due to the biological complexity of N ‐methyl‐ d ‐aspartate receptor ( NMDAR ), development a positron emission tomography radiotracer for imaging has met with limited success. Recent studies have established presence GluN2A subunit in heart and its role regulation intracellular calcium levels. In our efforts develop an agent subunit, we designed three new compounds based on quinoxaline scaffold. The synthesis analogues was two‐step Kabachnik–Fields reaction sequence Suzuki cross‐coupling...
In the pursuit of hydrophilic model fac ‐[Re(CO) 3 ] + complexes for (radio) pharmaceutical applications, six novel [2 1] mixed‐ligand general type (bid)P] were synthesized and characterized, where bid is a bidentate ligand bearing either (N, O) or (S, S′) donor atom sets P phosphine 1,3,5‐triaza‐7‐phosphoadamantane (PTA) its macrocyclic homologue 1,4,7‐triaza‐9‐phosphatricyclo[5.3.2.1]tridecane (CAP). The ligands used in this study picolinic quinaldic acid, while was diethyldithiocarbamate....