47 research outputs found
Comparaison de deux techniques de pré-purification des éluats de 68GA pour le marquage de peptides par automate de synthèse
In vivo 212Pb/212Bi generator using indium-DTPA-tagged liposomes
International audienceIndium-DTPA-tagged liposomes were studied in the present work as carriers of in vivo 212Pb / 212Bi generator to be used in targeted alpha therapy. The liposomal uptake of 212Pb, into preformed liposomes, was investigated using different lipophilic chelate (DCP, 2,3-dimercapto-1-propanol (BAL), sodium acetate, and A23187), as a function of various parameters (temperature, concentrations of lipids, Pb, DTPA,...) with 212Pb as a tracer. Different formulations of liposomes were tested to evaluate the radiolabeling efficiency. No complexing agent was necessary for the passage of Pb2+ through the membrane. It occurs naturally via a partial permeability of the lipid bilayer which increases with the temperature. A complexing agent (DTPA) appears necessary to concentrate Pb in the internal compartment of the liposomes. Conditions were found (T = 65°C, internal DTPA concentration of 0.025 M, pH 7.4, ...) yielding a high and rapid uptake of 212Pb in liposomes. The protocol established provides a novel method for the efficient entrapment of about 2-3 Pb atoms per liposome with a yield of 75% in conditions relevant for nuclear medicine
68Ga somatostatin analog radiolabelling: The radiopharmacist's point of view
68Ga-labelled peptides imaging has emerged during the last decade. This was possible thanks to innovative development in 68Ge/68Ga generator or bifunctional chelates (BFC) able to complex 68Ga and to be linked to various peptides and thus optimize radiolabelling procedures. This present review focuses on radiolabelling of somatostatine (SMS) analogs with 68Ga for clinical applications. In that sense, is discussed the key parameters influencing the radiolabelling, from the elution of 68Ge/68Ga generator to purification of final product, and through the quality control of 68Ga-SMS analog radiopharmaceuticals, as well as the full automation of the radiolabelling process
Ionic liquid supported organotin reagents for the manufacturing of radiopharmaceuticals compounds
Impact of DOTA Conjugation on Pharmacokinetics and Immunoreactivity of [177Lu]Lu-1C1m-Fc, an Anti TEM-1 Fusion Protein Antibody in a TEM-1 Positive Tumor Mouse Model.
1C1m-Fc, an anti-tumor endothelial marker 1 (TEM-1) scFv-Fc fusion protein antibody, was previously successfully radiolabeled with <sup>177</sup> Lu. TEM-1 specific tumor uptake was observed together with a non-saturation dependent liver uptake that could be related to the number of dodecane tetraacetic acid (DOTA) chelator per 1C1m-Fc. The objective of this study was to verify this hypothesis and to find the best DOTA per 1C1m-Fc ratio for theranostic applications. 1C1m-Fc was conjugated with six concentrations of DOTA. High-pressure liquid chromatography, mass spectrometry, immunoreactivity assessment, and biodistribution studies in mice bearing TEM-1 positive tumors were performed. A multi-compartment pharmacokinetic model was used to fit the data and a global pharmacokinetic model was developed to illustrate the effect of liver capture and immunoreactivity loss. Organ absorbed doses in mice were calculated from biodistribution results. A loss of immunoreactivity was observed with the highest DOTA per 1C1m-Fc ratio. Except for the spleen and bone, an increase of DOTA per 1C1m-Fc ratio resulted in an increase of liver uptake and absorbed dose and a decrease of uptake in tumor and other tissues. Pharmacokinetic models correlated these results. The number of DOTA per antibody played a determining role in tumor targeting. One DOTA per 1C1m-Fc gave the best pharmacokinetic behavior for a future translation of [ <sup>177</sup> Lu]Lu-1C1m-Fc in patients
Unprecedented Incorporation of alpha-Emitter Radioisotope 213Bi into Porphyrin Chelates with Reference to a Daughter Isotope Mediated Assistance Mechanism
For the first time, alphaemitter radioisotope 213Bi has been 10 incorporated into porphyrin chelates, with rates matching with the short period of the radionuclide. An in-situ transmetalation mechanism involving the daughter isotope 209Pb is expected to boost the 213Bi radiolabeling process.JRC.E.5-Nuclear chemistr
BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription
Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects. The etiological missense variants cluster in the amino-terminal region of human BCL11A, and we demonstrate that they all disrupt its localization, dimerization, and transcriptional regulatory activity, consistent with a loss of function. We show that Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype. Furthermore, we identify shared aberrant transcriptional profiles in the cortex and hippocampus of these mouse models. Thus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes.This article is available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.Wellcome Trust (grant number WT098051)Published (open access
Scandium-DOTA complexe for a new PET/3gamma camera for medical applications and radio labelling studies
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Scandium-DOTA complexe for a new PET/3gamma camera for medical applications and radio labelling studies
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Prospective comparison of FDG PET/CT and diffusion-weighted MRI for para-aortic metastases detection in cancer of the uterine cervix.
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