DOI: 10.1007/s10967-007-7244-6 Journal of Radioanalytical and Nuclear Chemistry, Vol. 279, No.1 (2009) 25–30
0236–5731/USD 20.00 Akadémiai Kiadó, Budapest
© 2008 Akadémiai Kiadó, Budapest Springer, Dordrecht
S-bridged complex of
99m
Tc with fac(S)-[Rh(aet)
3
]:
Quality control, characterization and biodistribution studies in rats
N. Amir,
1
* S. Roohi,
1
S. Pervez,
1
A. Mushtaq,
1
M. Jehangir,
1
Y. Miyashita,
2
K. Okamoto
2
1
Isotope Production Division, Pakistan Institute of Nuclear Science and Technology, P.O. Nilore, Islamabad, Pakistan
2
Department of Chemistry, University of Tsukuba, Tsukuba, 305-8571, Japan
(Received January 21, 2008)
fac(S)-[Rh(aet)
3
] (aet = 2-aminoethanethiolate) is N
3
S
3
metalloligand which can coordinate to transition metal ions to form S-bridged polynuclear
complexes. The reaction was carried out between
99m
TcO
4
Na and fac(S)-[Rh(aet)
3
] in the presence of SnCl
2
.
2H
2
O. A complex analogous to
[Re{Rh(aet
3
)}
2
]
3+
is formed.
6
A simple method for radiolabeling of fac(S)-[Rh(aet)
3
] with
99m
Tc has been developed and radiolabeling efficiency
was higher than 99%. Effect of SnCl
2
.
2H
2
O concentration, electrophoresis, HPLC, UV-Visible absorption spectra and biodistribution studies in
rats were performed. Higher uptake by kidneys showed rapid distribution of the labeled fac(S)-[Rh(aet)
3
]. Liver uptake was significant, stomach,
lungs and intestine uptake was high at 4 hours post injection time.
Introduction
Nuclear medicine is a branch of medical imaging
that uses radioactive tracers to examine the function of
body systems. The radionuclide used in about 90% of all
examinations is
99m
Tc, which is available from
99
Mo/
99m
Tc generators.
99m
Tc in some chemical form is
used in more than 85% of the diagnostic scans done
each year in hospitals. To reach targets in the human
body other than glandula thyreoidea,
99m
Tc needs a
carrier molecule, usually a chelating agent. Many
chelators that form stable complexes with
99m
Tc have
affinities for certain tissues in the human body. Other
chelators can be manipulated by pharmaceutical
formulation to be retained in certain body systems. In
order to form bonds with
99m
Tc, the chelator must
contain electron donors like N, O and S. Today,
chelators for the use with
99m
Tc exist for a number of
highly sensitive scintigraphic studies of the brain, heart,
skeleton, kidneys, hepatobiliary system and lungs. This
includes chelator such as dimercaptosuccinic acid, 1,2-
ethylenediylbis-L-cysteine diethyl ester, methylene-
diphosphonate, hexamethylpropylene-amineoxime and
hexakis(methoxy isobutylisonitrile).
1,2
The estrogen, progesterone and androgen receptors
may be useful for targeting breast and prostrate cancers.
The
99m
Tc labeling of progesterone receptor has been
studied utilizing conjugation to N
2
S
2
ligands via phenyl
spacer. An alternative approach is to integrate the
receptor binding sites directly onto the outer periphery
of the Tc ligands.
3,4
Bioconjugates of octreotide using
the N
2
S
2
ligand approach have been made for
99m
Tc and
have been investigated as a potential method for the
imaging of tumors. Steroids can be attached to rhenium
* E-mail: areena_a@hotmail.com
oxo-complexes of N
2
S
2
ligand systems in a directly
analogous fashion. This therefore is a promising
approach to the delivery of therapeutic radiation to
appropriate tumors.
5
The extensive investigations by numerous research
groups on a variety of N
2
S
2
and N
3
S donor type ligands
have revealed that the chemistries of these ligands with
Tc and Re are rather complex, giving rise to
considerable difficulties in the development of reliable
procedures for the development of radiopharmaceutical
reagents It is significant that thiolate based ligands
appear to offer considerable advantages in purity of
preparations and stability of the complexes. This led to
the development of a class of tridentate ligands, such as
bis(mercaptoethy1)methylamine (NS
2
), which may
constrain the possible coordination geometries and
improve overall stability.
6
Metalloligands, fac(S)-[M(aet)
3
] (M = Rh
III
, Ir
III
,
aet = 2-aminoethanethiolate) can react with transition
metal ions to form S-bridged polynuclear complexes.
These complexes indicated unique reactivity and
electrochemistry. Incorporation of Re ion into S-bridged
structure resulted in a fairly stable S-bridged complex
[Re{Rh(aet)
3
}
2
]
3+
. Investigations of redox properties
and stability of Re ion is important as fundamentals for
the application of Re compounds and development of
radiopharmaceuticals.
7,8
99m
Tc complexes are widely used for diagnostic
imaging. The chemistry of S-bridged metal complexes
has attracted much interest because of the importance of
the thiolato groups in a variety of systems ranging from
inorganic to organic and biological chemistry.
9,10
A number of complexes containing N and S donor
ligands have been reported and play an important role in
nuclear medicine. For example,
99m
Tc-L,L-ECD