New Tc-99m carbonyl complexes of SN bifunctional ligands [abstract]

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New Tc-99m carbonyl complexes of SN bifunctional ligands [abstract]

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Title: New Tc-99m carbonyl complexes of SN bifunctional ligands [abstract]
Other Titles: New Technetium-99m carbonyl complexes of SN bifunctional ligands
Author: Bhaskaran, Sharanya
Contributor: University of Missouri-Columbia. Office of Undergraduate Research
Keywords: cancer
Technetium-99m
ligand system
Date: 2004
Publisher: University of Missouri--Columbia. Office of Undergraduate Research
Abstract: Radiopharmaceuticals are drugs with two components: a radioactive element that delivers a dose of radiation to detect or kill cancer cells targeted by the radiopharmaceutical and a targeting molecule that seeks out cancer sites. Effective radiopharmaceuticals could be used for both the diagnosis and treatment of diseases such as breast cancer, prostate cancer, and various other cancers. The ideal radiochemical properties (E = 140 KeV), its optimum half life (t1/2 = 6.02 h) and ready availability make Technetium-99m one of the most attractive radioisotopes for use in imaging applications. For a radiopharmaceutical to be useful and effective for use under in vivo conditions, it is imperative to have high kinetic stability for the Technetium compounds and its bioconjugates. This presentation includes recent results on the design of a new chelating system towards the overall objective of the design and development of in vivo stable 99mTc complexes. Specifically, the new ligand system comprises two electron donors (Sulfur and Nitrogen centers - MeSCH2CH(COOH)NH2 ). This ligand system upon interaction with Technetium carbonyl (i.e. Tc in the +1 oxidation state) produced a well defined Tc carbonyl SN complex as shown below in > 90% yields. The TcSN complex demonstrated in vitro stability at pH 5-7 as evidenced by High Performance Liquid Chromatography (HPLC) analysis. The new TcSN complex still contained one unoccupied coordination site on the metal. This free site may result in further reactions of the Tc metal center with active ligands. In order to improve the kinetic inertness of the TcSN complex, tris (hydroxymethy phosphine) THP, P(CH2OH)3, was introduced to fill in the available sixth coordination site. The resulting TcSNP complex demonstrated good in vitro stability at pH 5-7 for over 24 hours as evidenced by the HPLC analysis. Further studies to utilize the carboxylate arm in TcSNP complex for conjugations with tumor specific peptides are underway. The coordination chemistry, radiochemistry, and in vitro stability studies will be discussed.
URI: http://hdl.handle.net/10355/555

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