A novel bifunctional chelating agent based on a click chemistry strategy has been synthesized and characterized on the basis of spectroscopic techniques. The metal chelating part of this new class of tridentate N2O ligand combined a triazole unit and an aromatic ring. This latter semi-rigid framework induced a pre-organization of the chelating cavity, improving the stability of the corresponding metallic complexes (M = (99m) Tc, Re). Thus, the (99m) Tc(CO)3 complex, obtained with good yield and excellent radiochemical purity (>90%), exhibited a high in vitro serum stability. Tissue biodistribution in normal mice showed a rapid clearance, no long-term retention in organs and no in vivo reoxidation of technetium-99m, making this compound a promising (99m)Tc-chelating system.
We present in this work a new technetium-99m-labeled derivative from isoniazid. The labeling was achieved with a double-ligand transfer through the use of a ferrocene derivative. A further referred to as 99mTc-N-IFC (N-Isonicotinamide ferrocene carboxamide labeled with 99mTc), targeting infections in experimental animals, has been synthesized. The N-IFC was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that it was obtained with high radiolabelling yield (95%). Radiochemical analyses of 99mTc-N-IFC revealed that the molecule was efficiently labeled with a little free pertechnetate in the preparations containing purified compound. Only 1–2% of the tracer was leached out from the complex at 24 h when incubated in serum at 37 ºC confirmed its high stability. The radiolabeled complex was found to be 10% bound to blood protein, which corresponds to a fast retention advantage. Biodistribution study showed the renal route of excretion and has also demonstrated that our radiolabeled compound is rapidly and significantly accumulated (P<0.5) at infection sites. Thigh model of localized infection was prepared in mice by injecting of BCG (pGFM-11) (fluorexcente BCG) live bacteria in growing phase. The confirmation of the bacteria presence in infection sites has been established through its fluorescence characteristic. The comparison of the 99mTc-N-IFC accumulation at sites of BCG (pGFM-11) infected animals, which is expressed as target-to-non-target ratio, (3.14) with other radiotracers was discussed. This allowed us to consider that 99mTc-N-IFC could be a good radiotracer for mycobacterial infections. Obtained results were in good and encourage to undergo a similar labeling for the Mycobacterium tuberculosis as perspective of this work.
The synthesis, characterization and biological evaluation of
N-Tolueneferrocenecarboxamide labeled with technetium-99m
(99mTc-TTCC) is reported. Biological studies in
Wistar rats showed the ability of 99mTc-TPCC to
cross the intact blood-brain barrier.
In vivo biodistribution
indicated that this complex had good brain uptake
(1.32% ID/g at 5 min and 0.64% ID/g
at 60 min) and good retention (about 50% of the
activity was retained in the brain at 60 min
post-injection). Regional brain distribution study showed that
hippocampus, where the 5-HT1A receptor density is high, had the
highest uptake (0.73% ID/g at 5 min p.i.) and
the cerebellum, where the 5-HT1A receptor density is low, had the
lowest uptake (0.12% ID/gID/g at 5 min
p.i.). After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the
uptake of hippocampus was decreased significantly from
0.73% ID/g to 0.20% ID/g at 5 min
p.i., while the cerebellum had no significant decrease. This result
indicates that 99mTc complex has specific binding to 5-HT1A receptor.
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