Improved titanium-44 purification process for establishing a high apparent molar activity titanium-44/scandium-44 generator

International audience44Sc-radiopharmaceuticals are gaining more interest but still lack availability. The proof of principle of a44Ti/44Sc generator, which can produce 44Sc daily, has been established but with some limitations and drawbacks. Despite recent advances, separation of 44Ti from massive quantities of scandium target material is still cumbersome. In this work, the improved radiochemical separation of 44Ti from residual scandium target material was carried out by precipitation of Sc with fluoride ions. Furthermore, two approaches were used to set up a high apparent molar activity small-scale generator. The first method relied on extraction chromatography for fine purification using a DGA resin, followed by loading of the purified 44Ti onto a ZR resin column. In the second method, 44Ti was loaded on the ZR resin directly after the precipitation step. This second method was used to set up a generator of 370 kBq and evaluate by radiolabeling. An apparent molar activity of 2 MBq/nmol was obtained for the radiolabeling with DOTA, the most common and suitable chelate for scandium. This result is comparable with previously published data on 44 m/44Sc. •Improved radiochemical purification of 44Ti isotope.•High apparent molar activity of small-scale (Horwitz et al., 2008)Ti/44Sc generator tested.•Eluted Sc-44 radiolabeled with DOTA without additional treatment

Development of scandium-exopolysaccharide complexes as a theranostic tool in bone oncology

International audienceThe anti-metastatic properties of an exopolysaccharide (EPS) derivative produced by a deep-sea hydrothermal bacterium, Alteromonas infernus, were favourably evaluated on bone remodeling [1]

A comparative thermodynamic study of the formation of scandium complexes with DTPA and DOTA

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Multimodal AGuIX® Nanoparticles: Size Characterization by HF5 and Optimization of the Radiolabeling with Various SPECT/PET/Theranostic Tracers

International audienceDiagnostics that combine imaging techniques such as PET and MRI could enhance disease detection and location if effective multimodal contrast agents can be developed. A nanoparticle called AGuIX has been developed that is comprised of gadolinium-bound by chelates and additional free chelates that can be further labelled with radioactive isotopes enabling both PET and MRI imaging. Herein, we describe the size characterization of these nanoparticles together with their size distribution, which is an important parameter for pharmacokinetics, by a hyphenated method that is hollow fiber flow field flow fractionation (HF5). Once radiolabeled, the size was determined to confirm their integrity. The average radius of these nanoparticles was about 3.5 nm and was not significantly affected by radiolabeling. The labeling of these nanoparticles with radionuclides for SPECT/PET was also evaluated (namely 64Cu, 44Sc and 67Ga). Parameters such as the molar ratio, pH and temperature were optimized. For the three radionuclides considered, 60% to 100% radiolabeling yields were reached, with no further purification at this stage. High specific activities could be attainable for all percentages of free DOTA grafted at the surface of the AGuIX nanoparticles considered in this work

Production of scandium radionuclides for theranostic applications: towards standardization of quality requirements

International audienceAbstractIn the frame of “precision medicine”, the scandium radionuclides have recently received considerable interest, providing personalised adjustment of radiation characteristics to optimize the efficiency of medical care or therapeutic benefit for particular groups of patients. Radionuclides of scandium, namely scandium-43 and scandium-44 (43/44Sc) as positron emitters and scandium-47 (47Sc), beta-radiation emitter, seem to fit ideally into the concept of theranostic pair. This paper aims to review the work on scandium isotopes production, coordination chemistry, radiolabeling, preclinical studies and the very first clinical studies. Finally, standardized procedures for scandium-based radiopharmaceuticals have been proposed as a basis to pave the way for elaboration of the Ph.Eur. monographs for perspective scandium radionuclides.</jats:p

Chemical and biological evaluation of scandium(III)-polyaminopolycarboxylate complexes as potential PET agents and radiopharmaceuticals

International audienceScandium isotopes (44Sc, 47Sc) are more available and their properties are convenient for either PET imaging or radiotherapy. To use them in nuclear medicine, ligands forming complexes with a high stability are necessary. Available experimental data on stability constants for complexes of ligands such as EDTA, DTPA, DOTA, NOTA and TETA with various metal ions have been published. But scandium is the exception since scarce data is available in the literature. Values of stability constants of Sc(III) with the ligands were determined by free-ion selective radiotracer extraction, complemented by 45Sc NMR and potentiometry data. The thermodynamic stability of the Sc-complexes increases in the order TETA < NOTA < EDTA < DTPA < DOTA. The in vitro stability of the Sc(III) complexes was studied in the presence of hydroxyapatite and rat serum to estimate their in vivo stability. The most stable complex was shown to be Sc-DOTA

Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI)

International audienceChitosan CS—tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity