Synthesis radiopharmaceutical

O-donor complexes that are currently used as Tc(V) precursors in the chemical and radiopharmaceutical synthesis are listed in Table 1. 

Table 1. TcOdigand),]" precursors used in the chemical and radiopharmaceutical synthesis of Tc(V) complexes...

Radiopharmaceutical Synthesis Time (minf Radiochemical Yield (%)b Ref... 

I8F]Fluoroacetone 84, a useful precursor in radiopharmaceutical synthesis, has been obtained101 from 86 with [18F]fluoride in MeCN (equation 48) in a sealed vessel. [18F]Carazolol 85 has been prepared as shown in equation 49. 

Because of the unique operational and safety requirements of radiopharmaceutical synthesis, the motivation for the development of automated systems is clear. These unique constraints include short synthesis times and control from behind bulky shielding structures that make both access to and visibility of radiochemical processes and equipment difficult. The need for automated systems is particularly expressed for PET radiopharmaceutical synthesis, with the short-lived radionuclides emitting high-energy y photons at 511 keV. Automated synthesis systems require no direct human participation. The short half-lives of the PET radionuclides may require repeated synthesis during the day, thus being a potential radiation burden for the operator when not using automated systems. 

Furthermore, radiopharmaceutical synthesis must be reliable and efficient and result in pharmaceutical-quality products. In addition, the processes must be well documented and controlled. Automated systems may support all these challenges and requirements. 

The position of the radionuclide in the molecule of interest is also critical as it will affect the biological behavior of the radiopharmaceutical. Chemical reactions must be designed to be stereospecific in many cases, as the production of a mixture of different stereoisomers complicates the purification of the final radiopharmaceutical. Synthesis procedures must also be easy to automate, as very elevated activities are used for the synthesis of PET radiopharmaceuticals (several curies usually) and appropriate radiation protection systems must be used. 

FIGURE 7 Automated synthesis module for PET radiopharmaceutical synthesis located in a shielded hot cell. (Photo courtesy of PET-CUN Center, University of Navarra.)... 

Kabalka, G.W. and Goodman, M.M. (1991). Synthesis of radiopharmaceuticals via organohoranes. In (ed. A.M. Emram), New Trends in Radiopharmaceutical Synthesis, Quality Assurance and Regulatory Control. Plenum Press, New York, NY. 

Because of these requirements, and in particular, the need to perform the reactions rapidly, it is not surprising that the application of microwaves was explored in the PET radiopharmaceutical synthesis area at an early stage [110]. However, the subsequent development did not match the rapid expansion in synthetic organic chemistry area in large part due to more stringent radiation safety considerations. 

Current Radiopharmaceutical Synthesis. The aqueous chemistry of technetium is dominated by the oxidizing power of soluble TcO , and the thermodynamic stability of insoluble TcOa. All technetium-99m radiopharmaceuticals, except pertechnetate itself, are prepared by the aqueous reduction of pertechnetate in the presence of a potential ligand to prevent Tc02 deposition (2). The most commonly employed reductant is stannous chloride, although many other reductants can, and have, been used (1,2). 

The only difference between the two preparations is the temperature at which the reduction is conducted at low temperatures the Tc(V) species TcOX is kinetically trapped and can be isolated, whereas at higher temperatures the Tc(V) complex suffers further reduction to yield the Tc(IV) species TcXg " (10,11). Other potential substances for radiopharmaceutical synthesis by substitution reactions include the undefined, reduced Tc-glucoheptonate complex (12) and the recently reported, lipophilic technetium(V) species Tc(HBPz Cl2 O (HBPz3 = hydrotris(l-pyra-zolyDborato ligand) (13). 

Homogeneous Reactions II Photochemistry and Electrochemistry and Radiopharmaceutical Synthesis... 

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