ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
SL4. The Use of 64-Cu in Radio-diagnostics and Radionuclide Therapy -
Required Properties of Chelators
M. J. Bjerrum . a , J. R. Holm-Jørgensen b , K. Jensen , M. Jensen c
a
Department of Natural Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871, Frederiksberg C,
Denmark,
b
Department of Natural Sciences, University of Copenhagen and Risø DTU, Thorvaldsensvej 40, DK-1871,
Frederiksberg C, Denmark
c
Risø National Laboratory for Sustainable Energy, Risø DTU, Technical University of Denmark,
Frederiksborgvej 399, DK-4000, Roskilde, Denmark
e-mail: mobj@life.ku.dk
Radiodiagnostics and radionuclide therapy are heavily investigated topics. The use of the same compound for
diagnostic and therapeutic purposes is highly desirable, and among the requirements are: tumor specificity, ease
and speed of isotope uptake and high inertia with respect to isotope expulsion. Possible candidate isotopes are
64 Cu (PET imaging and therapy) and 67 Cu (therapy). With copper radioisotopes there is a need for developing
novel chelators which forms kinetic and thermodynamic stable copper complexes. New candidates could be
adamanzanes, a class of macrobicyclic tetraamine ligands with unique copper binding properties. [1]
Cu(II) complexes are known for several of the adamanzane ligands. The uptake of Cu(II) is possible, choosing
the right conditions, and expulsion has been shown to be extremely slow from the native adamanzanes.
Furthermore, substituents on the non-bridged amine groups have been designed to function as linkers to a tumortargeting
protein, and this has been performed in our group with cytochrome c as the model protein. It has been
shown that it is possible to link the adamanzane ligand in a one-to-one ratio to one single protein site. It remains
to be shown if the inherent Cu binding stability of the adamanzane complex is retained. Knowing the structures
is essential to the interpretation of kinetic experiments necessary to prove the inertia with respect to Cu(II)
expulsion or other unwanted interactions under biological conditions.
References:
[1] Springborg J. Adamanzanes - bi- and tricyclic tetraamines and their coordination compounds. Dalton Trans.,
2003, 1653-1665.
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