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@INPROCEEDINGS{Buchholz:825285,
author = {Buchholz, Martin and Brandt, Marie and Vanasschen,
Christian and Spahn, Ingo and Coenen, Heinrich Hubert},
title = {{I}sotopic radiolabelling of the {MR}-contrast agent
{G}d-{DOTA} with {G}d-147/149},
reportid = {FZJ-2016-07749},
year = {2015},
abstract = {Objectives Due to the new multimodal capabilities of in
vivo imaging techniques, the supply of 147/149Gd appears
interesting for SPECT or autoradiographic imaging with the
aim to evaluate (new) MRI contrast agents. Although the
production of 147/149Gd by irradiation of Sm and Eu has been
published[1,2], an in vivo application of radiogadolinium
has hitherto not been reported. Also the isolation of
147,149Gd from the more effective target material Eu was not
described. Therefore, a bulk separation from the Eu target
material was developed, followed by the authentic labeling
of Gd-DOTA and a stability assessment of the complex in
human blood serum (HBS). Methods A described separation of
Sm2O3 and Gd2O3 with a Na-Hg amalgam[2] was systematically
adapted for the new target material Eu2O3. The influence of
extraction time, europium mass, amalgam mass and inert
atmosphere was assessed. The resulting Eu/Gd mixture was
absorbed on a DGA normal resin for the removal of excess
sodium with 1 M HNO3. The lanthanides were eluted
quantitatively with 0.1 M HCl, the resulting solution
reduced to dryness and taken up in 0.5 ml pure water.
Carrier-added and n.c.a.147/149Gd-DOTA was synthesized
within 20 min at 90°C in a 0.1 M NaOAc buffer at pH 4-6 and
the reaction monitored by radio-TLC. The stability of the
complex in HBS was investigated at 37°C over a time period
of 6 days. Results A $99.92\%$ reduction of the Eu
contamination down to 0.4 mg was achieved with the optimized
Na-Hg amalgam extraction without loss of 147/149Gd. This was
sufficient for first in vivo proof of principle tests with
147/149Gd-DOTA due to the strong chemical analogy of the
neighboring lanthanides Gd and Eu. Removal of excess sodium
was accomplished by a DGA resin enabling the application in
an animal model. Carrier-added and n.c.a. 147,149Gd-DOTA
were prepared with yields $>99\%.$ Additionally, over a time
period of 6 days no decomposition or ion leaching was
observed in HBS. Conclusions Bulk Eu was removed by amalgam
extraction from c.a. as well as n.c.a 147/149Gd which was
successfully used to label DOTA. This shows the possibility
of an authentic labeling of (new) MRI contrast agents,
allowing their in vitro or in vivo evaluation with
autoradiography or SPECT. Acknowledgements The authors
gratefully acknowledge the IKP-4 of FZJ for beam time and
all cyclotron operators. References [1] Denzler F.-O. et al.
(1997), Appl. Radiat. Isot., 48, 319. [2] Buchholz M. et al.
(2014), Appl. Radiat. Isot., 91, 8},
month = {May},
date = {2015-05-26},
organization = {21st International Symposium on
Radiopharmaceutical Sciences, Columbia
(USA), 26 May 2015 - 31 May 2015},
subtyp = {Plenary/Keynote},
cin = {INM-5},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {573 - Neuroimaging (POF3-573)},
pid = {G:(DE-HGF)POF3-573},
typ = {PUB:(DE-HGF)6},
url = {https://juser.fz-juelich.de/record/825285},
}