A. Mathur et al.
Partition coefficient (LogPo=w)
[
99mTcN(PNP5)]21 core, no significant improvement in the
uptake and retention of the prepared complexes in the
myocardium was obtained.
The HPLC-purified labeled compound (0.1 ml, 5 mCi) was mixed
with water (0.9 ml) and of octanol (1 ml) on a vortex mixer for
about 1 min and then centrifuged for 5 min to effect the
separation of the two layers. Equal aliquots of the two layers
were withdrawn and measured for the radioactivity. The
readings thus obtained were used to calculate the Log Po/w
value of the complex.
Acknowledgements
The authors are thankful to Prof. Adriano Duatti for providing
PNP6 ligand. The support and encouragement of Dr. V.
Venugopal, Director, Radiochemistry and Isotope group, BARC
is gratefully acknowledged.
Stability studies
Cysteine challenge. In challenge studies, purified fatty acid
complex (50 ml, 10 mCi), 10 mM cysteine solution (50 ml) and
saline (400 ml) were mixed in a 5-ml vial and incubated at 371C
for 30 min. Thereafter, the sample was analyzed by TLC [EtOH:
CHCl3: benzene: 0.5 M ammonium acetate (1.5:2:1.5:0.5) v/v] for
possible degradation of the original complex (11 carbon fatty
acid complex: Rf = 0–0.1, 12 carbon fatty acid complex:
Rf = 0–0.1).
Serum stability. To assess the stability of the fatty acid
complex in human serum, purified fatty acid complex (50 ml,
10 mCi) was incubated with human serum (450 ml) at 371C for
30 min. Thereafter, the serum proteins were precipitated by
addition of ethanol (500 ml), the solution was centrifuged, and
the supernatant was analyzed by TLC to determine the stability
of the complex in serum.
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In vivo evaluation studies
All procedures performed herein were in accordance with the
national laws pertaining to the conduct of animal experiments.
Normal Swiss mice (20–25 g body weight) were used for the
in vivo distribution studies. All the mice involved in the study
were kept under fasting condition for 6–7 h prior to the
experiment, with water given ad libitum. The HPLC-purified
radiolabeled preparation (100 ml, 20 mCi) was administered
intravenously through tail vein of each animal. Individual sets
of animals (n = 3) were utilized for studying the biodistribution
at different time points (2, 5, 10, and 30 min). The animals were
sacrificed immediately at the end of the respective time point
and the relevant organs and tissue were excised for measure-
ment of associated activity. The organs were weighed and the
activity associated with each was measured in a flat-bed type
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(140 keV710%). For the sake of comparison, the activity
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Two new positively charged fatty acid complexes with a
99mTcN(PNP6)]21 core were prepared and evaluated in
[
normal Swiss mice. Although the results obtained in this
study were similar to previously reported positively charged
fatty acid complexes labeled with
[
99mTcN(PNP3)]21 or
J. Label Compd. Radiopharm 2010, 53 580–585
Copyright r 2010 John Wiley & Sons, Ltd.