Fluorine-18: positron emission tomography

However, a body of evidence is being accumulated that if a halogen, such as a bromine or an iodine atom, is replaced by a beta-fluoroethyl group, the electronic and polar properties of the drug can be pretty much the same. So, what psychedelics have a bromo or an iodo group Obviously, DOB and DOI. Thus, DOEF is a natural candidate for fluorine-18 positron emission tomography, and also a natural candidate for clinical trials. And, voila, it is an active material. 

Positron emission tomography (PET) makes use of a short-lived positron emitter such as fluorine-18 to image human tissue with a degree of detail not possible with x-rays. It has been used extensively to study brain function (see illustration) and in medical diagnosis. For example, when the hormone estrogen is labelled with fluorine-18 and injected into a cancer patient, the fluorine-bearing compound is preferentially absorbed by the tumor. The positrons given off by the fluorine atoms are quickly annihilated when they meet... 

Considerable interest has been focused on the efficient and rapid synthesis of 2-deoxy-2-[ F]fluoro-D-gIucose, a popular imaging agent for positron-emission tomography (see Section III, 1). However, introduction of a fluorine atom at C-2 by nucleophilic displacement is generally not easy on account of the weak nucleophilic character of the fluoride ion. One possible... 

Yatham, L.N., Liddle, P. F. Dennie, J. (1999). Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment a positron emission tomography study with fluorine-18-labeled setoperone. Arch. Gen. Psychiatry, 56, 705-11. 

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... 

The next two chapters are dedicated to radiopharmaceutical contrast agents starting with a detailed description of the chemistry of p -emitting compounds based on fluorine-18. Particular emphasis is laid on the different radiolabeled precursors and their suitability for the rapid synthesis of compounds useful for positron emission tomography. 

Tamaki N, Yonekura Y, Yamashita K, Saji H, Magata Y, Senda M et al. Positron emission tomography using fluorine-18 deoxyglucose in evaluation of coronary artery bypass grafting. Am J Cardiol 1989 64 860-865... 

Gropler RJ, Geltman EM, Sampathkumaran K, Perez JE, Schechtman KB, Conversano A et al. Comparison of carbon-11-acetate with fluorine-18-fluorodeoxyglucose for delineating viable myocardium by positron emission tomography. J Am Coll Cardiol 1993 22 1587-1597... 

Fluorine-18 Chemistry for Molecular Imaging with Positron Emission Tomography... 

C. Halldin, T. Hogberg, L. Farde, Fluorine-18-labeled NCQ 115, a selective dopamine D-2 receptor ligand. Preparation and positron emission tomography, Nucl. Med. Biol. 21 (1994) 627-631. 

Most of the fluoro derivatives of proline described in the literature are fluorinated in the 4 position. 4-Fluoroprolines are able to mimic 4-hydroxyproline, present in some proteins and polypeptides. On the other hand, 4-fluorination could suppress oxidative metabolism or modified ring conformation of ligands.The labeled analogues may be used as probes in PET (positron emission tomography) for localization of tumors... 

Bhn J, Baron JC, Dubois B, et al Loss of brain 5-HT2 receptors in Alzheimer s disease in vivo assessment with positron emission tomography and fluorine-18 setoperone. Brain 116 497-510, 1993... 

Many fluorinations by electropositive fluorine reagents produce a-fluoro carbonyl compounds as the final result An extensive review exists on the preparation of a-fluorocarbonyl compounds [10]. Also, electropositive reagents are used, widely in the preparation ofISF-labeled radioactive materials required in positron emission tomography for biomedical research Excellent reviews are available on fluonne-18 labeling [11, 12]. 

Renewed interest in the fluorination of quaternary ammonium salts is prompted by the need for rapid fluorination techniques to incorporate 18F (t /f 110 mm) in positron emission tomography (PET) studies One promising approach is displacement of trimethylammomum ion, bound directly to an aromatic ring, by fluoride ion This technique was initially developed with substituted phenyltnmeth-ylammomum perchlorates and unlabeled cesium fluoride in dimethyl sulfoxide or acetonitrile [73] (equation 14)... 

The very short reaction times required for the alkylation of substrate 11a with benzylic bromides using Nobin as an asymmetric phase-transfer catalyst are important for the synthesis of 18F-fluorinated amino adds for use in positron-emission tomography (PET)-imaging studies. Thus, Krasikova and Belokon have developed a synthesis of 2-[18F]fluoro-L-tyrosine and 6-[18F]fluoro-L-Dopa employing a (S)-Nobin-catalyzed asymmetric alkylation of glycine derivative 11a as the key step, as shown in Scheme 8.14 [29]. The entire synthesis (induding semi-preparative HPLC purification) could be completed in 110 to 120 min, which corresponds to one half-life of18 F. Both the chemical and enantiomeric purity of the final amino acids were found to be suitable for clinical use. 

Fluorine is a chemical element that in pure form occurs as a dimer of two fluorine atoms, F2. The fluorine atom has the ground state electron configuration ls22s22p5. There is only one stable, naturally occurring isotope of fluorine 19F. However, the radioactive isotopes 17F, 18F, and 20F are known. The inclusion of the isotope 18F (half-life 110 minutes) in bioor-ganic molecules is an important noninvasive technique used in the study of living tissue by positron emission tomography. 

To monitor tumor response to capecitabine therapy noninvasively, Zheng and co-workers, from the Indiana University School of Medicine, developed the synthesis of the fluorine- 18-labeled capecitabine as a potential radiotracer for positron emission tomography (PET) imaging of tumors.28 Cytosine (20) was nitrated at the C-5 position with nitric acid in concentrated sulfuric acid at 85°C, followed by neutralization to provide 5-nitrocytosine (27) in moderate yield. This nitro pyrimidine was then carried through the glycosylation and carbamate formation steps, as shown in the Scheme below, to provide the 6/s-protected 5-nitro cytidine 28 in 47% for the three-step process. Precursor 28 was then labeled by nucleophilic substitution with a complex of 18F-labeled potassium fluoride with cryptand Kryptofix 222 in DMSO at 150 °C to provide the fluorine-18-labe led adduct. This intermediate was not isolated, but semi-purified and deprotected with aqueous NaOH in methanol to provide [l8F]-capecitabine in 20-30% radiochemical yield for the 3-mg-scale process. The synthesis time for fluorine-18 labeled capecitabine (including HPLC purification) from end of bombardment to produce KI8F to the final formulation of [18F]-1 for in vivo studies was 60-70 min. 

Adams S, Baum R, Rink T, Schumm-Drager PM, Usadel KH, Hor G (1989) Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumors. Eur J Nucl Med Mol Imaging 25,79-83. 

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