Séminaire spécialisé

jeudi 17 avril 2014 à 16:00

Amphi Charpak

Scandium complexes: physicochemical study and evaluation of stability in vitro and in vivo for nuclear medicine applications

Rabha Kerdjoudj

Subatech (groupe Radiochimie)

1- Objectives
Among the different isotopes of scandium, 47 Sc and 44Sc can be used in nuclear medicine. The 44Sc (3.97 h) decays in 94.27% of cases in emitting a positron [1], with a γ photon energy equal to 1.157 MeV. 44Sc has an isomeric state, 44mSc (T1/2=58.6h), co-produced with 44Sc that can be used as an in vivo 44mSc/44Sc generator. The high energy and high intensity ARRONAX cyclotron produces 44Sc together with its isomeric state 44mSc (T1/2=2.44 d) by the 44Ca (d, 2n)44,44mSc nuclear reaction to use as a potential in vivo PET generator. From our previous work [1], we have demonstrated that the DOTA chelator exhibits the highest complexation constant for Sc compared to other ligands such as DTPA, and NOTA. … In addition, the Sc(III)-DOTA complex is stable over several days in the presence of challenge by a bone mimic and rat serum. This study examines the physical-chemical effect of the decay of 44mSc to 44Sc of the radiolabeled DOTA complex with the goal of establishing experimentally the feasibility of 44mSc/44Sc as an in vivo generator.
Indeed, the longer half-life of 44mSc may enable imaging at later time points than currently achieved with the shorter lived common radionuclides of PET such as 11C, 18F , and Ga-68.…
2- Materials and Methods
The 44Sc and 44mSc are now commonly produced in ARRONAX. Scandium is purified with a column of DGA resin (Triskem, France) from the target by use of HCl 4M and eluted with HCl 0.5M. The radionuclidic purity was monitored by g -spectrometry and stable contaminants were determined by ICP-OES. The labeling conditions with DOTA were optimized and analyzed by Radio- TLC Flex Plate counted on a Cyclone (Perkin Elmer). To assess the feasibility of the in vivo 44mSc/44Sc generator, the resulting 44m/44Sc-DOTATATE was adsorbed onto a C18-Phenomenex Strata-X column which was eluted with DTPA to evaluate a potential scandium release. The radiolabeled ligand stability was evaluated in serum and challenged by a bone substitute.
3- Results
From 90% to 99 % of radiolabelling yields were obtained for metal-to-ligand ratio ranging from 1/1 to 10/1 respectively; in agreement with published data [1, 2]. The effect of pH, temperature and time was also examined. The elution from the C18-Phenomenex Strata-X
column showed that no release of scandium was observed at different time.
4 - Conclusions
This is the first experimental evidence that 44m/44Sc could be considered as an in vivo generator. Biological evidence is under investigation.


[1] Huclier-Markai, S, Sabatie, A., Ribet, S., Kubicek, V., Paris, M., Vidaud, C., Hermann, P.
and Cutler, C.S. [2011] Radiochim. Acta. 99: 653-662. [2] Majkowska-Pilip, A. and Bilewicz,
A. [2011] J. Inorg. Biochem. 105: 313-320.