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Technetium(I), Rhenium(I) Carbonil Complexes as New Radiopharmaceuticals


Study of Coordination Chemistry of Tricarbonyltechnetium(I) and Rhenium(I) Ions and Distribution of Their Complexes in Animals with Aim to Develop New Radiopharmaceuticals

Tech Area / Field

  • CHE-SYN/Basic and Synthetic Chemistry/Chemistry
  • MED-RAD/Radiomedicine/Medicine

8 Project completed

Registration date

Completion date

Senior Project Manager
Novozhilov V V

Leading Institute
Khlopin Radium Institute, Russia, St Petersburg

Supporting institutes

  • State Research Center – Institute of Biophysics, Russia, Moscow\nMinistry of Health / Central Research Institute of Roentgenology and Radiology, Russia, St Petersburg


  • Manchester Royal Infirmary, UK, Manchester\nPacific Northwest National Laboratory, USA, WA, Richland\nWashington University Medical Center / Mallinckrodt Institute of Radiology, USA, MO, Saint Louis\nUniversity of Illinois / School of Chemical Sciences, USA, IL, Urbana\nMAP Medical Technologies Oy, Finland, Helsinki

Project summary

The goal of this project is to reveal ways and to assess the possibilities of using tricarbonyltechnetium(I) and tricarbonylrhenium(I) complexes as radiopharmaceuticals for diagnostics and therapy. The species М(СО)32О)3+ (М= Тс, Rе) were prepared recently by a group of Swiss researchers; it is believed to be very promising for targeted transport of technetium and rhenium radioisotopes via the circulatory system to damaged tissues in the form of complexes with specific biomolecules. Its small size, low charge, and fac configuration may simplify its incorporation into the required small molecules and peptides without altering their function, and good solubility in water allows synthesis directly in aqueous solution.

This proposal is based on original single-stage preparation procedures developed by the authors, which allow synthesis of technetium(I) tricarbonyl halides directly in aqueous solutions with both weighable (99Тс, yield 100%) and trace (99mTc, yield >96%) amounts; in contrast to the existing methods, the resulting solutions contain no foreign substances (e.g., reducing agent and products of its oxidation). Therefore, it is possible not only to study complexation of the М(СО)3+ ion with various ligands in the absence of interfering species, but also to examine the behavior of various complexes of this ion in the organisms of laboratory animals without special pretreatment. The preliminary study performed at the Central Institute of Roentgenology and Radiology (St. Petersburg) and Institute of Biophysics (Moscow) showed that complexes of 99mTc(СО)3++ with some simple ligands are accumulated specifically in definite organs and tumors and therefore show promise for developing radiopharmaceuticals.

To accomplish the goal of the project, we intend:

(1) To optimize the synthesis of aqueous solution of technetium(I) tricarbonyl halide and determine the conditions for preparing the rhenium analog;

(2) To study the main features of coordination chemistry of М(СО)3+ ions in aqueous solutions, in particular, to determine the composition, stability, and structure of their complexes with relevant inorganic and organic ligands, with the aim of finding suitable coordinating groups for incorporation of the metal into peptide chains;
(3) To study with laboratory animals the accumulation address and the kinetics of uptake–clearance of a series of 99mTc(СО)3+ complexes with simple ligands, with the aim of using the results as basic data and testing the suitability of these complexes as radiopharmaceuticals;
(4) To develop schemes for incorporation of М(СО)3+ ions into various biomolecules and to study the effect of this procedure on the function of biomolecules in vivo.

In this study we will use the following methods. The composition, stability, and structure of М(СО)3+ complexes will be studied by potentiometric titration and IR, UV, and NMR spectroscopy, especially by 99Tc NMR spectroscopy which, according to our results, is a very efficient tool for studying technetium complexation in aqueous solutions. Complexation of 99mTc will be studied by TLC. In studies on nuclear medicine, along with traditional methods of biochemical analysis, we will use three-dimensional scintigraphy for imaging of radioisotope accumulation in laboratory animals.

Implementation of the product should result in elucidation of the main features of the coordination chemistry of М(СО)3+ ions (M = Tc, Re), choice of appropriate coordinating groups and scheme of incorporation of these ions into peptide chains of biomolecules, and obtaining of initial data for development of some radiopharmaceuticals based on these complexes.

Participation in the project of nuclear scientists working in the defense field will change their activity toward development of new radiopharmaceuticals for diagnostics and therapy.


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