ARRONAX GIP

Nantes, France

ARRONAX GIP

Nantes, France
SEARCH FILTERS
Time filter
Source Type

Huclier-Markai S.,ARRONAX GIP | Huclier-Markai S.,CNRS Laboratory of Subatomic Physics and Associated Technologies | Alliot C.,ARRONAX GIP | Alliot C.,University of Nantes | And 4 more authors.
RSC Advances | Year: 2015

The complexation of scandium(iii) by various polyaminopolycarboxylic ligands (DTPA and DOTA) was studied by capillary electrophoresis with ICP-MS detection in 0.1 mol L-1 NaCl ionic strength solutions at 25 °C. The results confirmed the formation of the 1:1 complexes for Sc(iii)-DOTA and Sc(iii)-DTPA systems. For each complex, the thermodynamic conditional constant was determined from the experimental data. The thermodynamic constants were extrapolated to zero ionic strength using the Davies equation and then compared to previously published data. These results were compared with free-ion selective radiotracer extraction (FISRE) data, which is a valid method for determining trace concentrations. The relative order of stability constants was preserved; as this method is experimentally simple, it is suitable for quick relative comparison of stability constant values under trace concentrations. © 2015 The Royal Society of Chemistry.


Kerdjoudj R.,CNRS Laboratory of Subatomic Physics and Associated Technologies | Pniok M.,University Karlova | Alliot C.,ARRONAX GIP | Alliot C.,University of Nantes | And 5 more authors.
Dalton Transactions | Year: 2016

The complexation ability of DOTA analogs bearing one methylenephosphonic (DO3AP) or methylenephosphinic (DO3APPrA and DO3APABn) acid pendant arm toward scandium was evaluated. Stability constants of their scandium(iii) complexes were determined by potentiometry combined with 45Sc NMR spectroscopy. The stability constants of the monophosphinate analogues are somewhat lower than that of the Sc-DOTA complex. The phosphorus acid moiety interacts with trivalent scandium even in very acidic solutions forming out-of-cage complexes; the strong affinity of the phosphonate group to Sc(iii) precludes stability constant determination of the Sc-DO3AP complex. These results were compared with those obtained by the free-ion selective radiotracer extraction (FISRE) method which is suitable for trace concentrations. FISRE underestimated the stability constants but their relative order was preserved. Nonetheless, as this method is experimentally simple, it is suitable for a quick relative comparison of stability constant values under trace concentrations. Radiolabelling of the ligands with 44Sc was performed using the radioisotope from two sources, a 44Ti/44Sc generator and 44mSc/44Sc from a cyclotron. The best radiolabelling conditions for the ligands were pH = 4, 70 °C and 20 min which were, however, not superior to those of the parent DOTA. Nonetheless, in vitro behaviour of the Sc(iii) complexes in the presence of hydroxyapatite and rat serum showed sufficient stability of 44Sc complexes of these ligands for in vivo applications. PET images and ex vivo biodistribution of the 44Sc-DO3AP complex performed on healthy Wistar male rats showed no specific bone uptake and rapid clearance through urine. © The Royal Society of Chemistry 2016.


Huclier-Markai S.,CNRS Laboratory of Subatomic Physics and Associated Technologies | Kerdjoudj R.,CNRS Laboratory of Subatomic Physics and Associated Technologies | Alliot C.,ARRONAX GIP | Alliot C.,University of Nantes | And 5 more authors.
Nuclear Medicine and Biology | Year: 2014

Introduction: Among the number of generator systems providing radionuclides with decay parameters promising for imaging and treatment applications, there is the 44Ti (T1/2=60years)/44Sc (T1/2=3.97h) generator. This generator provides a longer-lived daughter for extended PET/CT measurements compared to the chemically similar system 68Ge/68Ga. Scandium also exists as 47Sc, a potential therapeutic radionuclide. It is possible to produce 44Sc in a cyclotron using, for example, the 44Ca (d, n) 44Sc nuclear reaction. In that case, the isomeric state 44mSc (T1/2=58.6h) is co-produced and may be used as an in vivo 44mSc/44Sc generator. The aim of this study is to evaluate the feasibility of this in vivo 44mSc/44Sc generator and to demonstrate that the daughter radionuclide stays inside the chelator after decay of the parent radionuclide. Indeed, the physico-chemical process occurring after the primary radioactive decay (EC, IT, Auger electron ...) has prevented in many cases the use of in-vivo generator, because of the post-effect as described in the literature. Methods: The DOTA macrocyclic ligand forms stable complexes with many cations and has been shown to be the most suitable chelating moiety for scandium. Initially, the radiolabeling of DOTA and a DOTA-peptide (DOTATATE) with Sc was performed and optimized as a function of time, pH, metal-to-ligand ratio and temperature. Next, the physico-chemical processes that could occur after the decay (post-effect) were studied. 44mSc(III)-labeled DOTA-peptide was quantitatively adsorbed on a solid phase matrix through a hydrophobic interaction. Elutions were then performed at regular time intervals using a DTPA solution at various concentrations. Finally, the radiolabelled complex stability was studied in serum. Results: Radiolabeling yields ranged from 90% to 99% for metal-to-ligand ratio ranging from 1:10 to 1:500 for DOTA or DOTATATE respectively. The optimum physico-chemical parameters were pH=4-6, t=20min, T=70°C. Then, the 44mSc-DOTATATE complex, radiolabeled at 98%, was adsorbed through a hydrophobic interaction to a solid phase. Unlabeled scandium was completely eluted from the column whereas the Sc-DOTATATE complex was 100% retained. The release of 44Sc from the complex due to decay was less than 1% over 2 periods of 44mSc, independent of the DTPA concentration used for elution. 44mSc/44Sc-DOTATATE was stable in serum over 72h. Conclusions: The results indicate that the decay of 44mSc to 44Sc does not affect the integrity of the radiolabeled compound. Thus the 44mSc/44Sc generator is chemically valid and stable in serum. It could be used for PET imaging as an in-vivo generator increasing the life time of the scandium and allowing the use of antibody as labelled compound. Further in-vivo biological evaluations should complete this work. © 2014 Elsevier Inc.


PubMed | University of Nantes, CNRS Laboratory of Subatomic Physics and Associated Technologies and ARRONAX GIP
Type: | Journal: Nuclear medicine and biology | Year: 2014

Among the number of generator systems providing radionuclides with decay parameters promising for imaging and treatment applications, there is the (44)Ti (T1/2=60 years)/(44)Sc (T1/2=3.97 h) generator. This generator provides a longer-lived daughter for extended PET/CT measurements compared to the chemically similar system (68)Ge/(68)Ga. Scandium also exists as (47)Sc, a potential therapeutic radionuclide. It is possible to produce (44)Sc in a cyclotron using, for example, the (44)Ca (d, n) (44)Sc nuclear reaction. In that case, the isomeric state (44 m)Sc (T1/2=58.6h) is co-produced and may be used as an in vivo(44 m)Sc/(44)Sc generator. The aim of this study is to evaluate the feasibility of this in vivo(44 m)Sc/(44)Sc generator and to demonstrate that the daughter radionuclide stays inside the chelator after decay of the parent radionuclide. Indeed, the physico-chemical process occurring after the primary radioactive decay (EC, IT, Auger electron ) has prevented in many cases the use of in-vivo generator, because of the post-effect as described in the literature.The DOTA macrocyclic ligand forms stable complexes with many cations and has been shown to be the most suitable chelating moiety for scandium. Initially, the radiolabeling of DOTA and a DOTA-peptide (DOTATATE) with Sc was performed and optimized as a function of time, pH, metal-to-ligand ratio and temperature. Next, the physico-chemical processes that could occur after the decay (post-effect) were studied. (44 m)Sc(III)-labeled DOTA-peptide was quantitatively adsorbed on a solid phase matrix through a hydrophobic interaction. Elutions were then performed at regular time intervals using a DTPA solution at various concentrations. Finally, the radiolabelled complex stability was studied in serum.Radiolabeling yields ranged from 90% to 99% for metal-to-ligand ratio ranging from 1:10 to 1:500 for DOTA or DOTATATE respectively. The optimum physico-chemical parameters were pH=4-6, t=20 min, T=70C. Then, the (44 m)Sc-DOTATATE complex, radiolabeled at 98%, was adsorbed through a hydrophobic interaction to a solid phase. Unlabeled scandium was completely eluted from the column whereas the Sc-DOTATATE complex was 100% retained. The release of (44)Sc from the complex due to decay was less than 1% over 2 periods of (44 m)Sc, independent of the DTPA concentration used for elution. (44 m)Sc/(44)Sc-DOTATATE was stable in serum over 72 h.The results indicate that the decay of (44 m)Sc to (44)Sc does not affect the integrity of the radiolabeled compound. Thus the (44 m)Sc/(44)Sc generator is chemically valid and stable in serum. It could be used for PET imaging as an in-vivo generator increasing the life time of the scandium and allowing the use of antibody as labelled compound. Further in-vivo biological evaluations should complete this work.

Loading ARRONAX GIP collaborators
Loading ARRONAX GIP collaborators