Rhenium radiopharmaceuticals

Boschi A, Duatti A, Uccelli L (2005) Development of Technetium-99m and Rhenium-188 Radiopharmaceuticals Containing a Terminal Metal-Nitrido Multiple Bond for Diagnosis and Therapy. 252 85-115... 

Saladino R, Crestini C, Costanzo G, DiMauro E (2005) On the Prebiotic Synthesis of Nucle-obases, Nucleotides, Oligonucleotides, Pre-RNA and Pre-DNA Molecules. 259 29-68 Santos I, Paulo A, Correia JDG (2005) Rhenium and Technetium Complexes Anchored by Phosphines and Scorpionates for Radiopharmaceutical Applications. 252 45-84 Santos M, see Szathmdry E (2005) 259 167-211... 

The better known rhenium(V) chemistry is of great interest, not only because it resembles the second-row congener technetium and easily permits non-radio-active model studies for technetium. 186Re and 188Re are attractive isotopes for therapeutic radiopharmaceuticals. 99mTc and 186Re can be considered to be a matched pair for diagnostics and therapy. 

The need for and ethics of cancer therapy with radiopharmaceuticals are now being carefully discussed. The success in diagnosis of cancer using "Tc has provoked interest in the possibility of cancer therapy with radiorhenium. Even if complete recovery from the disease has not yet been achieved, positive changes in the quality of life (in about 80% of all patients) were reported by rhenium treatment for bone metastases. 

In the bifunctional radiopharmaceuticals, Tc and Re complexes that are suitable for coupling to antibodies are almost square-pyramidal oxo complexes of tetradentate ligands, as mentioned earlier. Spies et al. [65] recently studied the syntheses and structures of rhenium complexes with a tetradentate NS3 tripod ligand 2, 2,, 2"-nitrilotris(ethanethiol) (l in Fig. 9) as an interesting alternative to the oxo complex. Such ligands could lead to weakly polar, trigonal-bipyramidal complexes in which the metal atom is more strongly shielded than in the square-pyramidal oxo complexes. Schemes for the syntheses... 

The radiopharmaceutical chemistry of rhenium for cancer therapy is a new and developing field. The rapid increase in the numbers of papers concerned with i86, i88Re-compiexes for nuclear medicine unquestionably shows the importance of the chemistry of rhenium complexes, as mentioned by Deutsch in his lecture at the Fourth International Symposium on Technetium in Chemistry and Nuclear Medicine held in Bressanone, Italy in 1994. 

Despite such problems many people are now interested in the radiopharmaceuticals of rhenium. We hope the coming decade will be characterized by more successful applications of this therapy. 

These metals form chalcogenolate complexes in several oxidation states, and from the application-oriented point of view manganese compounds have been synthesized as models for hydrodesulfurization processes and rhenium and technetium derivatives as models for radiopharmaceuticals. 

Technetium and rhenium coordination chemistry has actively developed in order to design materials as potential radiopharmaceuticals diagnostic imaging agents for technetium and potential therapeutic reagents based on rhenium. Continuous efforts are still applied to find efficient chelating systems for the [MO]3+ cores (M=Tc, Re). Thus several complexes with monodentate and... 

This review is an inappropriate medium for a detailed discussion of rhenium coordination chemistry, but a brief summary of the trends is required as a background against which to set radiopharmaceutical developments, and is given below. 

The full exploitation of the wide range of oxidation states of rhenium in radiopharmaceutical design requires not only a wide range of ligand donor types with varied n-donor and acceptor properties, but also suitable reducing agents to provide access to oxidation levels below (VII). This is because for radiopharmaceutical purposes the most conveniently man-factured form of rhenium radionuclides is perrhenate. The traditional routes to reduced rhenium complexes are not particularly amenable to use in a radiopharmaceutical context, where mild, rapid, and preferably... 

Metal-essential radiopharmaceuticals are those whose targeting properties are inherent in the structure and chemistry of the complex itself rather than a biomolecule whose targeting ability is independent of the attachment of the metal. While this class of tracers includes many well-developed technetium complexes, it includes relatively few rhenium complexes. 

In this section the in vitro reactivity of various octahedral complexes of technetium and rhenium are discussed and correlated with the in vivo pharmacokinetic data as observed for currently used radiopharmaceutical agents, which in most cases are indeed octahedral complexes of these metal centers. 

Fig. 21. Comparison of half-lives. [Data from Table VII (equatorial ligand substitution, Table VIII (aqua substitution and related reactions) and Table IX (in vivo reactions of technetium and rhenium radiopharmaceuticals) of the complexes described in Section VII,A. Similar symbols denote similar technetium and rhenium complexes.]...

Half-Lives (37°C) of IN VIVO Reactions for Different Technetium and Rhenium Radiopharmaceuticals... 

By far, the largest number of structurally characterized rhenium complexes contain the metal in the oxidation state +5 . This can be attributed to the high stability of the rhenium(V) oxo, nitrido, and imido cores with a great variety of ligand systems, but is doubtlessly also related to the fact that rhenium complexes are frequently used as nonradioactive model compounds for the development of technetium radiopharmaceuticals. The dominance of 0 , and NR ligands can be... 

The chemistry of rhenium(I) is dominated by organometallic compounds which are not covered by this review. Thus, cyclopentadienyl and related compounds, where the organometallic part of the molecule dominate the properties will generally not be considered. Nevertheless, compounds with carbonyl or isocyanide co-ligands will be treated when they can be regarded as constituents of a typical coordination compound or the compounds are of fundamental interest in a radiopharmaceutical context such as the hexakis(isocyanide)rhenium(I) cations. For the same reason a separate section has been included which gives a brief summary of recent attempts to develop synthetic routes to tiicarbonylrhenium(I) complexes for nuclear medical applications. 

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