Book of Abstracts - Ruhr-Universität Bochum

P-55
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Synthesis and 99m Tc-Labeling of a PNA Oligomer Containing a New Ligand
Derivative of 2,2´-Dipicolylamine
Katrin Jäger, a Gilles Gasser, b Martin Zenker, a Ralf Bergmann, a Jörg Steinbach, a Holger Stephan, a
and Nils Metzler-Nolte b
a Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, Bautzner Landstrasse 128,
01314 Dresden, Germany. b Ruhr-University Bochum, Faculty of Chemistry and Biochemistry,
Department of Inorganic Chemistry I, Universitätsstrasse 150, 44801 Bochum, Germany.
E-mail: k.jaeger@fzd.de
The search for chelating ligands which can be efficiently labeled with radiometals, and which also
contain a functional group allowing a facile conjugation to biomolecules is currently a hot topic in
radiopharmacy. The 2,2’-dipicolylamine (Dpa) has already been found to be a good candidate for
labeling with 186 Re, 188 Re and 99m Tc 1 while the Cu(I)-catalyzed [2+3] azide/alkyne cycloaddition, often
referred to as Click Chemistry, 2 has been shown to be an effective coupling method. With this in mind,
we recently developed the facile synthesis of an azido derivative of Dpa (Dpa-N3, Figure 1). 3
Furthermore, as a proof of principle of the possible functionalization of our ligand to a biomolecule,
Dpa-N3 was successfully coupled, on the solid phase, to a ethinyl-substituted Peptide Nucleic Acid
(PNA) oligomer employing the Click Chemistry methodology to give the expected Dpa-ethyl-triazol-
PNA. Both Dpa-N3 and Dpa-ethyl-triazol-PNA could be efficiently labeled with 99m Tc using the
precursor [ 99m Tc(H2O)3(CO)3] + to afford [ 99m Tc(CO)3(Dpa-ethyl-triazol-N3)] + and [ 99m Tc(CO)3(Dpaethyl-triazol-PNA],
respectively. The radionuclide 99m Tc was tightly bound by the Dpa-chelator
avoiding the formation of pertechnetate for at least 24h. Partitioning experiments in a 1-octanol/water
system confirmed that both [ 99m Tc(CO)3(Dpa-N3)] + and [ 99m Tc(CO)3(Dpa-ethyl-triazol-PNA] are
rather hydrophilic. Biodistribution studies of [ 99m Tc(CO)3(Dpa-ethyl-triazol-PNA] in Wistar rats
showed a fast blood clearance and only a modest accumulation in the kidneys. Similar results were
found when a mouse model (NMRI nu/nu) was used.
N
N
N
N 3
N
(CO) 99m
3 Tc
N
Figure 1. Structures of Dpa-N3(left) and [ 99m Tc(CO)3(Dpa-N3)] + (right).
References
1. T. Storr, C. L. Fisher, Y.Mikata, S. Yano, M. J. Adam, C. Orvig, Dalton Trans., 2005, 654-655.
2. M. V. Gil, M. J. Arévalo, Ó. López Synthesis, 2007, 11, 1589-1620.
3. G. Gasser, K. Jäger, M. Zenker, R.Bergmann, J. Steinbach, H. Stephan, N. Metzler-Nolte, 2010,
submitted.
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N 3
+