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V17n8a04 PDF
V17n8a04 PDF
Freie Universitt Berlin, Institute of Chemistry and Biochemistry, Fabeckstrae 34-36, D-14195 Berlin, Germany
b
Institute of Inorganic Chemistry, University of Zrich, Winterthurerstrae 190, CH-8057 Zrich, Switzerland
Compostos de coordenao do elemento radioativo tecncio so empregados para diagnstico
em medicina nuclear, sendo vrios complexos do nucldeo emissor de radiao 99mTc usados
rotineiramente na obteno de imagens de rgos. As tendncias modernas da qumica
radiofarmacutica concentram-se na marcao de molculas biologicamente ativas tais como
peptdeos, esterides ou outras espcies com receptor especfico. Por esta razo necessrio
conhecer melhor a qumica de coordenao deste metal de transio artificial, especialmente
no que diz respeito s esferas de coordenao estveis ou inertes que possibilitam o acoplamento
a biomolculas, de acordo com a estratgia de formao de bioconjugados. O papel dominante
dos compostos de tecncio nos procedimentos de diagnstico sugere o uso dos istopos do
rnio emissores de radiao , 186Re e 188Re, para fins teraputicos em medicina nuclear. O
istopo 188Re facilmente obtido a partir do istopo 188W, e as abordagens sintticas empregadas
na qumica do tecncio podem ser investigadas para a obteno dos complexos de rnio.
Coordination compounds of the radioactive element technetium are well established in
diagnostic nuclear medicine, and various complexes of the -emitting nuclide 99mTc are routinely
used for organ imaging. Modern trends in the radiopharmaceutical chemistry of technetium
focus on the labeling of biologically active molecules such as peptides, steroids or other
receptor-seeking units. This requires more knowledge about the coordination chemistry of the
artificial transition metal, particularly with regard to stable or kinetically inert coordination
spheres, which allow couplings to biomolecules following a bioconjugate approach. The dominant
role of technetium compounds in diagnostic procedures recommends the -emitting rhenium
isotopes 186Re and 188Re for applications in nuclear-medical therapy. 188Re is readily available
from an 188W/188Re radionuclide generator system and general synthetic approaches can be
adopted from the established technetium chemistry.
Keywords: technetium, rhenium, coordination chemistry, nuclear medicine, bioconjugates
1. Introduction
As members of group 7 of the Periodic Table, the
elements with the atomic numbers 43 (technetium) and
75 (rhenium) possess a rich coordination chemistry. This
covers eight different oxidation states and various ligand
systems reaching from almost pure electron donors, such
as oxo or imido ligands to systems with pronounced backdonating properties such as carbonyls or isocyanides.1,2
The organometallic chemistry of the two elements is well
established as well as the chemistry of compounds with
metal-metal bonds.3
Despite the fact that technetium has no stable isotopes
(see Scheme 1) the chemistry of this artificial element is
*e-mail: abram@chemie.fu-berlin.de
1487
Scheme 1.
-, , 66h
(86 %)
99mTc
-, , 66h
(14 %)
, 6h
99Tc
-, 2.12 x 105 a
99Ru
(stable)
Scheme 2.
1488
Scheme 3.
Figure 1. Complexone-type ligands, which are used in classical 99mTc radiopharmaceuticals for imaging of kidney, liver and bone.
O
O
NH
1489
HN
H2O, heating
NH
HN
99m
TcO4-, SnCl2, O2
N O
Tc
S
HN
SH
O
COOH
HN
O
COOH
O
COOH
O
P
O
O
CH2 O
O P O
Tc
Tc
O
Tc
O
O P O
O
H
O
CH2 O
O
OH
H
O
O
H
O
O
P O
CH2 O
P
O
P
O
Scheme 4.
O
Tc
CH2 O
O P O
Tc
O
O
HO
H
O
O
1490
OMe
EtO
EtO
P
P
EtO
O
Tc
O
OEt
EtO
OMe
OEt
N
N
Tc
H
Tc complexes.
OMe
S
Tc
S
N
H
C
S
MeO
Cl
Figure 3. Heart-seeking
OMe
OMe
N
O
Me
OEt
Tc
B
O
N
P
EtO
99m
MeO
MeO
Me
H5C2COOC
NH
Tc
N
1491
O
H
A
Figure 4. Brain-seeking
99m
Tc complexes.
Tc
Tc
S
COOC2H5
1492
Figure 5. Rhenium complexes, which mimic the structures of the steroids dihydrotestosterone, progesterone and estradiol (upper row).
H3C N
Tc
Tc
NH
Figure 6.
99m
OMe
Cl
Tc
N
COOMe
Cl
A
S
N
N
N
N
O
Tc based radiopharmaceuticals for imaging of the neuronal dopamine transporter (A and B) and the serotonergic 5-HT1A ligand WAY (C).
1493
Scheme 5.
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M = Tc, Re
HN
O
(4 + 1)
(3 + 2)
NH
N
R
O
M
N
(3 + 1)
(4 + 1)
O
R
P N
O
P
Cl
A
S
R
N
C
H
N
Figure 7. Examples of mixed-ligand complexes of technetium and rhenium for the labelling of biomolecules.
O
NH R
HN
OH
HN
O
O
M
N
HN
NH2
HO
NH
NH
O
HO
HO
OH
NH R P(C6H4SO3Na)3,
N
O
L=
M = Tc, Re
PPh(C6H4SO3Na)2,
PPh2(C6H4SO3Na)
L
SO3H
M
OH
HO
NH
COOH
O
C
Figure 8. 6-Hydrazinonicotinic acid (A) and examples of HYNIC complexes with tricine and various hydrophilic ternary ligands.
1495
Scheme 6.
HN
S
S
N
OC
NH2
O
OC
OC
CO
CO
CO
OC
N
HN
N
OC
OC
CO
M
F
CO
OC
CO
M
X
OC
H3COOC
OC
CO
S
OC
CO
F
OC
CO
CO
NH
G
M = Re, Tc; X = Cl, Br
Figure 9. Tricarbonylrhenium(I) and -technetium(I) complexes with potential for radiopharmaceutical applications.
1496
Cl
Re
Cl
Re
OC
Cl
NO
CO
(NMe4)Cl
OC
CO
CH2Cl2, rt
OC
NO
H2O (H+) + Y
Y = NOBF4,
OC
or NaNO2,
or NOHSO4
M
NO
OC
2
X
M
X
CO
Scheme 7.
[ReOCl3(Ph3P)2]
or
[NBu4][MOCl4]
Me
Me
R N
N R
R
N
R
THF, (H2O)
N
R
M = Tc, Re
Me
Me
R N
N R
R
N
O
Re
H2O
(H2O)
R
N
N
N
R
N
R
N
R
with R = Me, Et, i-Prop
N
R
THF
N
R
R
N
O
Cl
2+
R
N
N
R
R
MeOH
N
R
N
R
with R = Me, Et
N
R
Scheme 8.
R
N
O
Re
OMe
2+
N
R
N
R
with R = Me
1497
Scheme 9.
O
NH2
NH2
NH2
HN
HOOC
Ph3P
Cl
O
Re
Cl
PPh3
NH2
Ph3P
Cl
N
Re
Cl
PPh3
Cl
Cl
B
L
Me
Me
RN
NR
Scheme 10.
N
Re
L
L
N
L
Re
L
Cl
Cl
1498
Scheme 11.
7. Conclusions
It is obvious from the previous sections that
coordination chemistry plays an important role in the
development of novel rhenium and technetium radiopharmaceuticals. Although kit preparations for the
imaging of almost all main organs and organ systems exist
and there is some experience in the labeling of
biomolecules, there is still a need for new approaches and
new labeling procedures. Many of the routine methods
apply the same or related chelator systems and oxidation
states of the transition metals. This strongly restricts the
opportunities to influence specific properties of the metalbiomolecule conjugates.
It will remain a challenge for synthetic chemists to supply
novel methods and compound for the radiopharmaceutical
community. Promising contributions are expected from the
coordination chemistry as well as from the organometallic
chemistry of these two group VII elements.
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