Radiopharmaceuticals development

Research and Development Radiopharmaceutical Business Line Institute of Isotopes Co., Ltd. Konkoly Thege M. Street, 29-33 1121 Budapest, Hungary... 

Large pharmaceutical companies focus on developing blockbuster drugs with sales of billions of dollars. They are not interested in developing radiopharmaceuticals for small numbers of patients in whom molecular imaging makes possible personalized, custom-tailored therapy. They believe, erroneously, that the market is too small to justify the approval costs. This is true today, but will not be in the future. 

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... 

Until the mid 1970s, technetium(V) had been widely ignored and its chemistry misinterpreted. Then, the development of the chemistry of technetium(V) was prompted by the trends and needs of nuclear medicine, which predominantly uses technetium-99m radiopharmaceuticals for a broad range of diagnostics. 

The development of 99mTc-radiopharmaceuticals offers many challenges, since this metal is not a component of any naturally occurring biological... 

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. 

Due to the clinical availability of Octreoscan , the first peptide-based receptor-imaging radiopharmaceutical, there has been much interest in the development of a complimentary therapeutic radiopharmaceutical.89... 

Dilworth, J. R. Parrott, S. J. Developments in Nuclear Medicine. 1996, 30 (Current Directions in Radiopharmaceutical Research and Development), 1-29. 

The standard work of Evans [2] as well as a survey of the papers produced in the Journal of Labeled Compounds and Radiopharmaceuticals over the last 20 years shows that the main tritiation routes are as given in Tab. 13.1. One can immediately see that unlike most 14C-labeling routes they consist of one step and frequently involve a catalyst, which can be either homogeneous or heterogeneous. One should therefore be able to exploit the tremendous developments that have been made in catalysis in recent years to benefit tritiation procedures. Chirally catalyzed hydrogenation reactions (Knowles and Noyori were recently awarded the Nobel prize for chemistry for their work in this area, sharing it with Sharpless for his work on the equivalent oxidation reactions) immediately come to mind. Already optically active compounds such as tritiated 1-alanine, 1-tyrosine, 1-dopa, etc. have been prepared in this way. 

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... 

The development of PET radiopharmaceuticals labeled with generator-produced radionuclides has facilitated greater use of PET in clinical nuclear medicine. The 68Ge/68Ga parent/daughter pair is ideal as a source of PET radiopharmaceuticals as a result of the favorable half-lives of both the parent and daughter radionuclides (43-45). The 271 days half-life of the 68Ge parent... 

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. 

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. 

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