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Abstract  

The organometallic precursor of fac-[99mTc(CO)3(H2O)3]+ has attracted much attention because of the robustness and small size of Tc(I)-tricarbonyl complexes compared to Tc(V) complexes and the good labeling affinity with a variety of donor atoms. Among various ligand systems, an iminodiacetic acid (IDA) was proven as a good chelating group to form a Tc(III)-compelx as well as has been shown its potential as a chelating system for fac-[99mTc(CO)3] precursor. In an attempt to confirm the similarity and the difference between 99mTc(CO)3-IDA and 99mTc-(IDA)2-complex, M(CO)3-IDA (M = 99mTc, Re) complexes of disofenin, mebrofenin and N-(3-iodo-2,4,6-trimethyl phenylcarbamoylmethyl) iminodiacetic acid were prepared, and the biological evaluation of 99mTc(CO)3-disofenin was performed. The 99mTc(CO)3-IDA complexes were prepared with a high radiolabeling yield (>98%) in a quantitative manner and showed a negative charge. The in vivo pharmacokinetic behavior of 99mTc(CO)3-disofenin showed a similar biological activity to 99mTc-(disofenin)2 in that those complexes were quickly cleared from the blood by the hepatocytes and excreted into the gallbladder and intestine. Accordingly, the 99mTc(CO)3-IDA derivatives of disofenin and mebrofenin might be used as hepatobiliary imaging agents. Since an IDA is a promising chelator for 99mTc-based radiopharmaceutical and the biological properties of 99mTc(CO)3-IDA derivative shows similar to that of 99mTc-complex, a biomolecule containing IDA can be freely radiolabeled with fac-[99mTc(CO)3]-precursor or 99mTc. However, the radiolabeling efficiency and the biological behavior demonstrates the favorable properties of 99mTc(CO)3-IDA compound for the development of a new imaging agent.

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Abstract  

Reactions of carbonate (CO 3 –· ) and bicarbonate (HCO 3 · ) radicals generated by photolysis of a carbonate or bicarbonate solution at pH 11.2 and 8.5, respectively, with Co(II) complexes of iminodiacetic acid (IDA) and ethylenediaminetetraacetic acid (EDTA) have been studied. The rate constants for the reactions were in the order of 106–107 dm3mol–1s–1. From the time-resolved spectroscopy of the products formed after reaction of CO –· or HCO 3 · , it is observed that CO 3 –· or HCO 3 · oxidize the metal center to its higher oxidation state.

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Abstract  

This work reports the synthesis, radiolabeling and preliminary biodistribution results in tumor-bearing mice of [99mTc(CO)3(IDA–PEG3–CB)]. The novel chlorambucil derivative was successfully synthesized by conjugation of iminodiacetic acid (IDA) to chlorambucil via a pegylated linker. The ligand could be labeled by [99mTc(CO)3]+ core in high yield to get [99mTc(CO)3(IDA–PEG3–CB)], which was very hydrophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that [99mTc(CO)3(IDA–PEG3–CB)] accumulated in the tumor with favorable uptake and retention. The good accumulation in tumor tissue with high tumor/muscle ratios warrants further research to improve tumor targeting efficacy and pharmacokinetic profile of radiolabeled chlorambucil derivative by structural modification.

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