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@ARTICLE{Kopp:282875,
author = {I. Kopp and P. Cieslik and K. Anger and T. Josephy and L.
Neupert and G. Velmurugan and M. Gast and H. Wadepohl and S.
A. Brühlmann and M. Walther and K. Kopka$^*$ and M.
Bachmann and H. Stephan and M. Kubeil and P. Comba},
title = {{B}ispidine {C}helators for {R}adiopharmaceutical
{A}pplications with {L}anthanide, {A}ctinide, and {M}ain
{G}roup {M}etal {I}ons.},
journal = {Inorganic chemistry},
volume = {62},
number = {50},
issn = {0020-1669},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {DKFZ-2023-01877},
pages = {20754-20768},
year = {2023},
note = {2023 Dec 18;62(50):20754-20768},
abstract = {Octadentate and specifically nonadentate ligands with a
bispidine scaffold (3,7-diazabicyclo[3.3.1]nonane) are known
to be efficiently coordinated to a range of metal ions of
interest in radiopharmaceutical chemistry and lead to
exceedingly stable and inert complexes. Nonadentate
bispidine L2 (with a tridentate bipyridine acetate appended
to N3 and a picolinate at N7) has been shown before to be an
ideal chelator for 111In3+, 177Lu3+, and 225Ac3+, nuclides
of interest for diagnosis and therapy, and a
proof-of-principle study with an SSTR2-specific octreotate
has shown potential for theranostic applications. We now
have extended these studies in two directions. First, we
present ligand derivative L3, in which the bipyridine
acetate is substituted with terpyridine, a softer donor for
metal ions with a preference for more covalency. L3 did not
fulfill the hopes because complexation is much less
efficient. While for Bi3+ and Pb2+ the ligand is an
excellent chelator with properties similar to those of L2,
Lu3+ and La3+ show very slow and inefficient complexation
with L3 in contrast to L2, and 225Ac3+ is not fully
coordinated, even at an increased temperature $(92\%$
radiochemical yield at 80 °C, 60 min, [L3] = 10-4 M). These
observations have led to a hypothesis for the complexation
pathway that is in line with all of the experimental data
and supported by a preliminary density functional theory
analysis, which is important for the design of further
optimized bispidine chelators. Second, the coordination
chemistry of L2 has been extended to Bi3+, La3+, and Pb2+,
including solid state and solution structural work, complex
stabilities, radiolabeling, and radiostability studies. All
complexes of this ligand (La3+, Ac3+, Lu3+, Bi3+, In3+, and
Pb2+), including nuclides for targeted α therapy (TAT),
single-photon emission computed tomography, and positron
emission tomography, are formed efficiently under
physiological conditions, i.e., suitable for the labeling of
delicate biological vectors such as antibodies, and the
complexes are very stable and inert. Importantly, for TAT
with 225Ac, the daughter nuclides 213Bi and 209Pb also form
stable complexes, and this is important for reducing damage
to healthy tissue.},
cin = {DD01},
ddc = {540},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37707798},
doi = {10.1021/acs.inorgchem.3c02340},
url = {https://inrepo02.dkfz.de/record/282875},
}