F-labeled Compounds

The synthesis of2-deoxy-2- F-fluoro-D-glucose (2-[ F]FDG) [153-155] is another example where the application of microwaves can reduce the synthesis time and increase the radiochemical yields. An initial optimization of the standard nucleophilic fluorination with mannose triflate under microwave conditions cut short 

Nucleophilic aliphatic radiofluorination with tosylate as leaving group. 

The reduction of reaction time and improvement in RCYs by microwave enhancement are of great advantages in the synthesis of radiopharmaceuticals involving multiple steps. In certain cases, the synthesis of the secondary labeling agent was accelerated so that the time saved could be diverted to the next step, or in other 

The synthesis of 2-(4-[ F]fluorophenyl)benzimidazole represents another example of the latter strategy [160]. Cydocondensation of an aromatic diamine with an aliphatic add using microwave heating proceeds rapidly the same reaction using aromatic and sterically hindered alkyl adds requires more vigorous conditions (e.g. 

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In a comparative study, [ F]FDHR, the well-known extractable MBF SPECT (single photon emission computed tomography) tracer p° TI]TICI, and the vascular reference tracer [ l]albumin were evaluated in 22 isolated erythrocyte- and albumin-perfused rabbit hearts. A superior retention of [ F]FDHR was observed and the net uptake of this F-labeled compound was better correlated with the blood flow than that of p° TI]TICI, indicating that [ F]FDHR is a better flow tracer than p° TI]TICI in isolated rabbit hearts [72]. 

PET imaging of cardiac sympathetic innervation with 6-p F]FDA was evaluated in healthy volunteers regarding its safety, efficacy, validity, and significance. As a conclusion, the uptake of 6-[ F]FDA reflects the distribution of cardiac sympathetic innervation, and the tracer represents a suitable F-labeled compound for... 

This chapter will focus on the (1) main indications of [ F]-FDG-PET and -PET/ CT and (2) the innovative [ F]-labeled compounds in oncology. 

Acetamido-2-deoxy-D-glucose is a component of a mucopolysaccharide hyaluronic acid. It has been demonstrated, by PET imaging with the corresponding F labeled compound, that this glucose derivative is incorporated into the connective tissue at the interface of a tumor and healthy tissue. Thus, it can be used as a tumor label. 6-[ F]-6-Deoxy-L-ascorbic acid also deserves attention, as it maintains the antioxidant properties of ascorbic acid. Thus, it can be useful to smdy the biochemical... 

Aromatic fluorination A new method of aromatic fluorination involves treatment of aryltriazenes, readily prepared from aryldiazonium ions and dialkyl-amines, with 70% hydrogen fluoride in pyridine. The yields of product from this reaction are usually higher than those obtained by the reaction of HF-pyridine with a diazonium ion (6, 285) o-methoxy, iodo-, bromo- and nitro-substituted aryltriazenes generally give unsatisfactory yields. This method may be useful for the synthesis of " F-labeled compounds. 

By nucleophilic substitution or electrophilic fluorination a great variety of F-labelled compounds are synthesized for application in nuclear medicine, such as 2-[ F]fluoro-2-deoxy-D-glucose, L-6-[ F]fluoro-3,4-dihydroxyphenylalanine (l-6-[ F]fluoro-DOPA), 3-N-[ F]fluoroethylpiperone and many others. For labelling by nucleophilic substitution, F must be applied free of water in a polar aprotic solvent. For that purpose, water is removed by distillation in the presence of large... 

These results proved to be of utmost value for the synthesis of the F-labelled compounds for positron emission tomography. The speed with which the addition and subsequent separations could be achieved experimentally enabled the 2- F-glucose to be obtained with a radioactive purity of over 98% and with high specific activity, eg. 

The aspect of a reversible reaction of fluorinase was of major importance for further optimizations and by addition of the enzyme L-amino acid oxidase (L-AAO) the oxidative removal of formed L-methionine was enabled. In this way, the equilibrium of the reaction was pulled toward 5 -[ F]FDA and allowed very high radiochemical yields of 95% within 1-2 h. Accordingly, the F-labeled compounds 5 -[ F]fluoro-5 -deoxyinosine (5 -[ F]FDI) (O Fig. 42.30h), 5 -[ F]fluoro-5 -deoxyribose phosphate (O Fig. 42.30c)y and 5 -[ F]fluoro-5 -deoxyribose (O Fig. 42.30d) were successfully produced from 5 -[ F]fluoro-5 -deoxyadenosine (Deng et al. 2006, Onega et al 2009, 2010). In the base-swap strategy, the 5 [i F]fluoro-5 -deoxyribose phosphate O Fig. 42.30c) could be further transformed into... 

Hot-atom chemistry of a number of fluorocarbons [perfluoro-n-hexane, -cyclohexane, -(methylcyclohexane), -cyclohexene, -benzene, and -toluene] has been studied, the substrates being activated by means of the nuclear reactions F(n,2n) F and F(y,n) F a large number of F-labelled compounds were obtained, but, except in the case of perfluoro-n-hexane (suggested displacement reactions C,Fi4 + F -+ CjFjs F + F- C,Fi4 + > F- -> CsF i F + CF,- C,Fi4 + F- - CjF. F + CsF,-), most of the radioactive products were not recognized. 

Rowland, F.S., Cramer, J.A., Iyer, R.S., Milstein, R., Williams, R. L., "Synthesis of F-Labelled Compounds by Direct Reactions of Atomic F in Radiopharmaceuticals and Labelled Compounds", Vol. 1, International Atomic Energy Agency, Vienna, 1973. 

SCHEME 45.14. Application of fluorinase in the production of [ F]-labeled compounds. 

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