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Journal of Radioanalytical and Nuclear Chemistry
Authors: M. Jovanović, J. Brborić, S. Vladimirov, B. Zmbova, LJ. Vuksanović, D. Živanov-Stakić, and V. Obradović

Abstract  

A new diiodine substituted IDA derivative, 2,4-diiodine-6-methyl IDA (DIIODIDA) was synthesized and labeled with99mTc. It was established that99mTc-DIIODIDA had high radiochemical purity. Biodistribution and influence of bilirubin on99mTc-DIIODIDA biokinetics has been studied in rats and compared to the corresponding results for99mTc-SOLCOIODIDA. Related to99mTc-SOLCOIODIDA,99mTc-DIIODIDA has much better biliary exretion (55.18 versus 43.63%). No change of99mTc-DIIODIDA biokinetics, under influence of bilirubin was noticed. Biliary excretion of99mTc-SOLCOIODIDA has been reduced for about 60%. The protein binding of99mTc-DIIODIDA and99mTc-SOLCOIODIDA were also determined, using in vitro method of precipitation. These results showed that99mTc-DIIODIDA hepatobiliary imaging agent is superior to the presently used99mTc-monoiodine IDA derivatives.

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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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