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Technetium Chemistry at High Oxidation States: New Opportunities for the Development of Radiopharmaceuticals

Applicant Braband Henrik
Number 143102
Funding scheme Ambizione
Research institution Institut für Chemie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Inorganic Chemistry
Start/End 01.10.2012 - 30.09.2013
Approved amount 129'114.00
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Keywords (6)

nuclear waste deposition; nanomaterials; radiochemistry ; radiopharmaceutical chemistry; nanomedicine; technetium

Lay Summary (English)

Lead
Lay summary

Technetium is an important element for society. Its long-lived isotope technetium-99 (99Tc) is a fission product in nuclear power plants (production worldwide ca. 3000 kg / year) and a challenging task for nuclear waste management, due to its long half-life (2.13·105 years). Furthermore, the meta-stable nuclear isomer 99mTc is a common radio tracer for nuclear medical diagnostics. The availability of this nuclear isomer from generators, in combination with the short physical half-life time (6 h) and the emission of low energy gamma-rays (140.5 keV) make 99mTc a very convenient and practical isotope. To pave the way for new opportunities in 99mTc radio probe design and to generate new impulses for technetium chemistry in general, the field of water stable fac-{99(m)TcO3}+ complexes has been developed. The reactivity of fac-{99(m)TcO3}+ complexes with alkenes (vicinal cis-dihydroxylation reaction by (3+2)-cycloaddition) plays a central role in this novel technetium chemistry. This project develops the chemistry of {99(m)TcO3}+ compounds further and aims at the advancement of this chemistry from the level of fundamental research to utilization.

An important issue for the development of labeling procedures which are based on the reactivity of fac-{99mTcO3}+ complexes with alkenes is the control of the stereo-chemistry of the (3+2)-cycloaddition reaction. The project will give detailed insights about factors which influence the stereo-chemistry of the (3+2)-cycloaddition and will lead to reactions, which are under full stereo-control. Furthermore, the reactivity and stability of (3+2)-cycloaddition products, which carry an additional functional group to the glycolato unit will be studied. Finally, to widen the scope for the development of new imaging probes a nanoplatform suitable for molecular imaging will be realized.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
High-valent Technetium Chemistry - New Opportunities for Radiopharmaceutical Developments
Braband Henrik, High-valent Technetium Chemistry - New Opportunities for Radiopharmaceutical Developments, in Journal of Labelled Compounds and Radiopharmaceuticals .

Collaboration

Group / person Country
Types of collaboration
PD Dr. Dominik Brühwiler / Zürcher Hochschule für Angewandte Wissenschaften Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
5th International Workshop on „Coordination Chemistry of Metals with Medical Relevance and Supramolecular Building Blocks“, Freie Universität Berlin, Institute of Chemistry and Biochemistry Talk given at a conference 18.07.2013 Berlin, Germany Braband Henrik;
RheManTec II Talk given at a conference 23.02.2013 Saas Grund, Switzerland Braband Henrik;


Associated projects

Number Title Start Funding scheme
126414 Technetium Chemistry at High Oxidation States: New Perspectives for Nanomaterials and Polyoxometalates in Medicine and Environmental Science 01.10.2009 Ambizione

Abstract

Technetium is an important element for society. Its long-lived isotope technetium-99 (99Tc) is a fission product in nuclear power plants (production worldwide ca. 3000 kg / year) and therefore a challenging task for nuclear waste management, due to its long half-life of 2.13x10exp(5) years. Furthermore, the meta-stable nuclear isomer 99mTc is a common radio tracer for nuclear medical diagnostics. The availability of this nuclear isomer from generators, in combination with the short physical half-life time (6 h) and the emission of low energy gamma-rays (140.5 keV) make 99mTc a very convenient and practical isotope. To pave the way for new opportunities in 99mTc radio probe design and to generate new impulses for technetium chemistry in general, a new field of water stable fac-{TcO3}+ complexes was developed in the last years. The reactivity of fac-{TcO3}+ complexes with alkenes (vicinal cis-dihydroxylation reaction through a (3+2)-cycloaddition) is a central point of this new field of technetium chemistry. The knowledge gained in the time of this Ambizione project enables a multitude of new opportunities. However, to bring this new type of technetium chemistry from the level of fundamental research to application, a few more objectives have to be accomplished.The control of the stereo-chemistry of the (3+2)-cycloaddition reaction of fac-{TcO3}+ complexes with alkenes is an essential issue for the development of labeling procedures based on this new strategy. This objective will give detailed insights into factors which influence the stereo-chemistry of the (3+2)-cycloaddition and will lead to reactions, which are under full stereo-control. In the same context, the stability of the (3+2)-cycloaddition products has to be evaluated. In the objective cis-trans-interconversion of (3+2)-cycloadducts the stability and reactivity of (3+2)-cycloaddition products, which carry an additional functional group to the ‘diolato’-unit will be studied. It was already shown that additional functional groups are important to control the stereo-selectivity of the (3+2)-cycloaddition reaction. Knowledge gained by this research will not exclusively influence the development of new radiopharmaceuticals but also the development of new procedures for the synthesis of trans-hydroxilated organic compounds. To widen the scope for the development of new imaging probes a nanoplatform, suitable for molecular imaging will be realized. The demonstrated flexibility of the new labeling strategy in the center of this follow-up proposal will establish a complementary procedure for the development of new imaging probes and will bring this strategy form the level of fundamental research to application. Finally, this follow-up proposal aims at the sustainable establishment of basic education in nuclide chemistry and radiation protection at the University of Zurich. This will bring forward the aim to extend the number of students with experience in these important fields.
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