Study of Carbonyl Complexes
Synthesis and Study of Technetium (I) and Rhenium (I) Hydrophilic Carbonyl Complexes and Radiopharmaceuticals on their Basis
Tech Area / Field
- CHE-SYN/Basic and Synthetic Chemistry/Chemistry
3 Approved without Funding
Khlopin Radium Institute, Russia, St Petersburg
- University of Helsinki / Department of Clinical Radiochemistry and Radiochemistry, Finland, Helsinki
Project summaryThe work is aimed at studying coordination chemistry of technetium(I) and rhenium(I) carbonyl complexes with the ultimate goal of preparing new 99mTc and 186Re radiopharmaceuticals. The published data on coordination chemistry of technetium(I) and rhenium(I), including results obtained by the participants of this project, allow setting up a work on preparation of a broad series of water-soluble carbonyl complexes of these elements with various donor-active species. However, proper development and tests of new radiopharmaceuticals require certain stages to be passed. These stages, which are formulated below, form the contents of our project.
In the first stage, we wish to study behavior of known technetium and rhenium carbonyl complexes toward water and to prepare new hydrophilic complexes, including complexes with biologically important compounds. Despite numerous reports on the synthesis of carbonyl complexes of technetium and especially rhenium, most of the complexes prepared are neutral hydrophobic compounds. Technetium and rhenium carbonyl complexes were studied, as a rule, in the crystalline state or non-aqueous solutions; data on behavior of these complexes in aqueous solutions are almost lacking. At the same time, such data are required for creating new radiopharmaceuticals, since they are usually used as aqueous solutions and will occur in an aqueous medium inside a living body.
In this stage, experiments will be performed with macroamounts of long-lived 99mTc and natural rhenium. As the main synthesis method, we will use a method that has been previously developed by participants of the project and is based on carbonylation of inorganic technetium and rhenium compounds with carbon monoxide generated directly in the autoclave. The methods will be improved in order to curtail the synthesis duration and ensure single-stage synthesis of organic derivatives of the carbonyl complexes. We will also examine the feasibility of preparing these compounds at atmospheric pressure. For identification of the compounds, we will use conventional methods of macrochemistry - elemental analysis, IR and NMR spectroscopy, and X-ray diffraction.
The second stage of the study, which is the key stage, will involve passing to microamounts of short-lived 99mTc and 186Re. The main goals of this stage are development of quick methods for preparing technetium and rhenium carbonyl complexes (in view of short half-lives of these nuclides, 6h and 3.78 days respectively). Furthermore, the methods should yield the target products as aqueous solutions suitable for injection. The synthesis, at least in the case of technetium, should take no more than 4h and be single-stage wherever possible; it should start from compounds that are directly produced in isotope generators, i.e., from pertechnetates or perrhenates. Furthermore the composition of the final aqueous solution with respect to macrocomponents should meet requirements imposed on solutions for injections, i.e., the solution should not contain appreciable amounts of toxic substances, and its pH should be close to neutral.
From the methodological viewpoint, an important problem of this stage is development of methods for indirect identification of chemical forms of short-lived technetium and rhenium on the basis of their distribution or chromatographic behavior using radiometric methods of analysis. For this purpose, we should first study behavior of macroamounts of corresponding complexes under analysis conditions. The principal problem of this stage is to examine the applicability of results obtained with macroamounts of compounds to trace amounts, which do not form an intrinsic phase.
The final stage of the study will involve medicobiological tests of new technetium and rhenium carbonyl complexes and formulation of recommendations on the use of technetium and rhenium carbonyl complexes in nuclear medicine.
Studies within the framework of this project will result in synthesis of a series of new (primarily hydrophilic) technetium and rhenium complexes. Their compositions will be determined, and their structures will be studied. New data will be obtained on behavior of the complexes in aqueous solutions, which will allow prediction of transformations of the complexes within a living body. For a number of complexes, quick synthesis methods will be developed in order to prepare the complexes of short-lived nuclides (99mTc and 186Re) in trace amounts and ensure the composition of the aqueous phase with respect to macrocomponents that would meet requirements to solutions for injections. Medicobiological behavior of 99mTc and 186Re complexes will be studied. On the basis of the above results, recommendations will be formulated for use of technetium and rhenium carbonyl complexes as radiopharmaceuticals.
Potential Contribution of Non-CIS Collaborators
In view of the fact that in Western countries medicobiological studies of 99mTc and 186Re complexes are performed much more extensively than in Russia and the assortment of corresponding radiopharmaceuticals is much broader, the main role of foreign collaborators may consist in formulation of recommendations on choice of particular biologically active compounds to be incorporated into technetium and rhenium carbonyl complexes and provision with these compounds.
The International Science and Technology Center (ISTC) is an intergovernmental organization connecting scientists from Kazakhstan, Armenia, Tajikistan, Kyrgyzstan, and Georgia with their peers and research organizations in the EU, Japan, Republic of Korea, Norway and the United States.
ISTC facilitates international science projects and assists the global scientific and business community to source and engage with CIS and Georgian institutes that develop or possess an excellence of scientific know-how.