Tracers fluorine

Rowland, F. S. Cramer, J. A. Iyer, R. S. Milstein, R. Williams, R. L., "Chemical Reactions of Atomic Fluorine Atoms, as Studied with Tracer Fluorine-18," Nippon Aisotopu Kaigi Hobunshu 1973,11,360. 

A PET scan requires a substance called a tracer. A suitable tracer must accumulate in the target organ, and it must be modified to contain unstable radioactive atoms that emit positrons. Glucose is used for brain imaging, because the brain processes glucose as the fuel for mental and neural activities. A common tracer for PET brain scans is glucose modified to contain radioactive fluorine atoms. Our molecular inset shows a simplified model of this modified glucose molecule. 

Table 8.47 shows the available options for the analysis of polymer processing aids, namely combustion and instrumental methods. The best method is dependent on PPA type, the level to be measured, and the available equipment (see also Section 8.2.1.2). Fluoropolymer processing aid concentrations can be determined by WDXRF configured to measure either fluorine or a tracer, and by EDXRF to analyse a tracer [29]. Calibration curves are required. At present, EDXRF or benchtop XRF units cannot directly measure fluorine. For resin or masterbatch producers who prefer to make on-line XRF measurements of processing aid concentrations (to letdown levels of 50-100 ppm), processing aids that contain a tracer (usually BaS04) are available. The analysis time is less than two minutes. 

When radon is heated to 400°C with fluorine, a nonvolatile fluoride is formed (Fields et al., 1962, 1963). It has been deduced from the chemical behavior that the product is radon difluoride, RnF2. (Products of the tracer experiments have not been analyzed because of their small mass and intense radioactivity.)... 

Aromatic fluorination can be carried out by a regiospecific destannylation process shown in reaction 69. This is an effective method for producing fluorinated m-tyrosine and other radiopharmaceuticals, as shown in reaction 70. The process can be applied for radiolabelling with 18F, denoted as F in these reactions, and the products used as radioactive tracers for clinical and fundamental investigations318-321. 

The choice of an isotope for tracer studies requires an appreciation of not only the radiochemical properties of the element, but also the effects that they might have both biochemically and analytically. The isotope should have a half-life that is long enough for the analysis to be completed without any significant fall in its activity. Occasionally this might present a problem in that some elements only have radioactive isotopes with very short half-lives, e.g. fluorine-18 has a half-life of 111 min. Conversely, isotopes with very long half-lives should not be used for in vivo studies because accumulation in the tissues of the recipient is unacceptable. 

The main radiopharmaceuticals labelled with fluorine-18, routinely prepared ([2-i F] fluorodeoxyglucose [ F]FDG [26-28], [i F]fluoro-L-DOPA [29], [i F]altanserin [30, 31], [ F]setoperone [32]) are presented with their uses in Table 2. For comparison, the most common tracers labelled with carbon-11 (methionine [33], palmitic acid [34], flumazenil (RO 15.1788) [35], PK 11195 [36], raclopride [37], deprenyl [38], Way-100635 [39], McN-5652Z [40], CGP 12177 [41]) are shown in Table 3. By far, [ F]FDG is the most widely studied, particularly in oncology for the diagnosis of tumours, detection of sub-clinical diseases, assessment of therapy responses, and detection of recurrence. F-Steroids [42], F-proteins or peptides, or F-labelled tissue specific agents have also been synthesized for the detection and monitoring of various malignancies [43]. 

Figures 1 and 2 compare the uses (oncology vs receptors) of tracers labelled with carbon-11 and with fluorine-18 [44].

The introduction of F in a tracer molecule can be used to block metabolism as,for example, with [ F]FDG,or to detect metabofic processes. Introduction of a fluorine also changes the fipophilidty of the compound. Correlations between hpophihcity (log P) and the abifity of a labelled compound to cross the blood brain barrier has been measured by PET (as an example see [59]). 

Introduction of a fluorine-18 in )0-position to the pyridine nitrogen has been carried out in 37 % radiochemical yield by nucleophilic exchange for NO2 in the synthesis of a potential MAO-B imaging tracer (Scheme 48) [205]. 

Ding Y-S, Eowler JS (1996) 18F-Labeled tracers for positron emission tomography studies in the neurosciences. In Ojima 1, McCarthy J, Welch JT (eds) Biomedical frontiers of fluorine chemistry. ACS Symp Series 639. The American Chemical Society, Washington DC, chap 23, p 328... 

J. Bergman, O. Solln, Fluorlne-18-labeled fluorine gas for synthesis of tracer molecules, Nucl. Med. Biol. 24 (1997) 677-683. 

J. Mukherjee, Z.Y. Yang, M.K. Das, T. Brown, Fluorinated benzamide neuroleptics-lll. Development of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[ F]fluoropropyl)-2,3-dime-thoxybenzamide as an improved dopamine D-2 receptor tracer, Nucl. Med. Biol. 22 (1995) 283-296. 

Table 1. Different fluorine-labeled PET tracers with their functional targets...

The radiosynthesis starts with the nucleophilic F-fluorination of 2-benzyloxy-4-formyl-A/,A/,A/-trimethylanilinium trifluoromethanesulfonate or 5-benzyloxy-2-nitrobenzaldehyde. Subsequent condensation with nitroethane yielded the corresponding 2-nitro-1-propanol derivatives. Reduction of the nitro moiety and deprotection provided the four stereoisomers of " F-labeled 2-amino-1-(4-fluoro-3-hydroxyphenyl)-1-propanol and 2-amino-1-(2-fluoro-5-hydroxyphe-nyl)-1-propanol, respectively. 4-p F]FMR was isolated from the 2-amino-1-(4-fluoro-3-hydroxyphenyl)-1-propanol stereoisomer mixture via semipreparative HPLC and additional chiral HPLC for enantiomeric resolution. In a similar manner enantiomeric pure 6-p F]FMR was obtained. From a synthetic point of view, 4-p F]FMR appeared to be the more promising candidate for PET investigations due to higher radiochemical yields. The main advantage of the nucleophilic approach over the electrophilic methods is the obtained high specific radioactivity (56-106 GBq/pmol) that is desired for safe use in humans with tracer doses far beyond the pharmacological level [173]. 

In addition to CFCs and their replacements, there are some fully fluorinated compounds that are emitted to the atmosphere during various industrial processes, including the manufacture of HCFCs and HFCs. Because of the strong C-F bonds, these compounds have long atmospheric lifetimes (e.g., see Cicerone, 1979 and Ravishankara et al., 1993) and hence have been used as tracers to determine the age of stratospheric... 

Compounds containing 02 cation 340 are colorless with the exception of 02+PtF6, which is red due to the PtF6 ion. The compound 02+PF6 decomposes slowly at 80°C862 and rapidly at room temperature, giving oxygen, fluorine, and phosphorous pentafluoride. 18F tracer studies on 02+BF4 have led to the conclusion that the mechanism of the decomposition involves the equilibrium [Eq. (4.216)] followed by a bimolecular decomposition of 02F.863... 

The above novel radiofluorinated derivatives of benperidol have been synthesized to improve the selectivity for binding to D-2 receptors in the course of identifying a fluorine-18 labelled tracer. 

Dihydroxyphenylalanine (DOPA) (99) is produced by tyrosine hydroxylase-catalyzed hydroxylation of Tyr. Recent interest in the use of [18F]-6-F-DOPA (100) as a PET scanning agent for regional dopaminergic brain function is based on its conversion, in the brain, to [,8F]-6-F-dopamine (101)161. The fact that fluorine in the 6-position of DOPA, dopamine and other catecholamines retards methylation by catechol-O-methyl transferase presumably increases the biological half-life of the tracer. In contrast, fluorine in the 5-position increases the rate of methylation162. 

Since radon has only a short half-life, study is difficult, but tracer studies allow some properties to be deduced, for example, the formation of RnF2, RnF+TaF, and possibly Rn03. Oxidation of Rn by C1F3 and study on a fluorinated ion-exchange material (Nation) suggests that Rn+ can displace Na+ or K+. 

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