Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Publisher Summary This chapter provides an overview of the 13 Carbon-nuclear magnetic resonance ( 13 C-NMR) spectroscopy of monosaccharides. The 13 C-NMR spectroscopy has become increasingly important as a tool for the characterization and structural elucidation of sugars and their derivatives. Although 13 C-NMR is closely related to 1 H-NMR spectroscopy, especially when both types of spectra are recorded with Fourier-transform instruments, the two techniques are sufficiently different to be valuable complements to each other. In many cases, in particular when dealing with complex molecules such as polysaccharides, the amount of information obtainable from 1 H-NMR spectra is limited as compared to that revealed by 13 C- NMR spectra. This chapter provides an almost complete collection of 13 C- NMR chemical shifts of monosaccharides, their methyl glycosides, and acetates, along with the examples of shift data for as many different types of monosaccharide derivative as possible. It also provides details on sampling techniques and assignment techniques, and discusses the identity of monosaccharides, their structure determination, and conformational analysis .

Carbon-13 Nuclear Magnetic Resonance Spectroscopy of Monosaccharides

Molecular Imaging with PET

In recent years, tools for the development of new drugs have been dramatically improved. These include genomic and proteomic research, numerous biophysical methods, combinatorial chemistry and screening technologies. In addition, early ADMET studies are employed in order to significantly reduce the failure rate in the development of drug candidates. As a consequence, the lead finding, lead optimization and development process has gained marked enhancement in speed and efficiency. In parallel to this development, major pharma companies are increasingly outsourcing many components of drug discovery research to biotech companies. All these measures are designed to address the need for a faster time to market. New screening methodologies have contributed significantly to the efficiency of the drug discovery process. The conventional screening of single compounds or compound libraries has been dramatically accelerated by high throughput screening methods. In addition, in silico screening methods allow the evaluation of virtual compounds. A wide range of new lead finding and lead optimization opportunities result from novel screening methods by NMR, which are the topic of this review article.

Drug Discovery Today

The many facets of the oxytocin (OXT) system of the brain and periphery elicited nearly 25,000 publications since 1930 (see FIGURE 1, as listed in PubMed), which revealed central roles for OXT and ...

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The Oxytocin Receptor: From Intracellular Signaling to Behavior

1516 Objectives (R,S) Anti-1-amino-2-[18F]fluorocyclopentyl-1-carboxylic acid (18F-FACPC) has been reported as a potent tumor-detecting agent for positron emission tomography (PET). Our in vitro and in vivo 9L tumor studies indicated that 18F-FACPC was transported via system L and showed high tumor uptake.1 The goal of this study was to evaluate, in vitro, the transport properties of that tracer isolated enantiomers and their suitability for tumor detection. Methods 16 and 17 were prepared from their precursors 14 and 15, by no-carrier-added nucleophilic substitution. A comparison of uptake studies of 18F-FACPC and its enantiomers was performed in 9L gliosarcoma cells. The biological behavior of 16 and 17 was further evaluated in vitro, using human glioma (U87MG) and different types of human breast cancer, MDA mb 231, mb 435, and mb 468. Results 16 and 17 were obtained in an average decay-corrected yield of 25% (n=5) and enantiomeric purity of > 90%. The absolute configurations of 16 and 17 have not been confirmed yet. They will be referred to, as peaks 1 and 2, corresponding to their order of appearance on a chiral column. The in vitro assays performed using 9L gliosarcoma cells in the presence of inhibitors of amino acid transport, BCH, MeAIB, and ACS demonstrated that 16 and 17 are substrates for system L with peak 1 showing higher accumulation in tumor (12%) than peak 2 (7%). The in vitro assays performed using U87MG, MDA mb231, mb 435, and mb 468 cancer cells showed that, in the absence of inhibitors, peak 1 displayed tumor uptakes of 28%, 9%, 4%, and 7% comparing to peak 2, 17%, 6.4%, 2.6%, and 5.3%, respectively. Moreover, these results confirm the transport of 16 and 17 with system L. Conclusions 16 and 17 are useful amino acids for the diagnosis of cancer using PET. Peak 1 shows significantly higher cell uptake and may be a more powerful tool as a tumor-detecting agent for PET, especially for the imaging of a brain cancer. Research Support 1. N. Jarkas, R. V. Voll, V. M. Camp, L. Williams, E. Malveaux, and M. M. Goodman. J. Labelled Cpd. Radiopharm., 2009; Suppl. 1; S19

Characterization of the two enantiomers of anti-18F-FACPC as PET tumor agents

Syntheses and biological activities of novel 2-methoxyestradiol analogs, 2-fluoroethoxyestradiol and 2-fluoropropanoxyestradiol, and a radiosynthesis of 2-[18F]fluoroethoxyestradiol for positron emission tomography

[18F]2-Fluoroethyl-p-toluenesulfonate also called [18F]2-fluoroethyl tosylate has been widely used for labeling radioligands for positron emission tomography (PET). [18F]2-Fluoroethyl-4-bromobenzenesulfonate, also called [18F]2-fluoroethyl brosylate ([18F]F(CH2)2OBs), was used as an alternative radiolabeling agent to prepare [18F]FEOHOMADAM, a fluoroethoxy derivative of HOMADAM, by O-fluoroethylating the phenolic precursor. Purified by reverse-phase HPLC, the no-carrier-added [18F]F(CH2)2OBs was obtained in an average radiochemical yield (RCY) of 35%. The reaction of the purified and dried [18F]F(CH2)2OBs with the phenolic precursor was performed by heating in DMF and successfully produced [18F]FEOHOMADAM, after HPLC purification, in RCY of 21%. Copyright © 2013 John Wiley & Sons, Ltd.

Synthesis of a phenolic precursor and its efficient O-[18F]fluoroethylation with purified no-carrier-added [18F]2-fluoroethyl brosylate as the labeling agent.

PURPOSE: 8-(2-[18F]fluoroethyl)-2β-carbomethoxy-3β-(4-chlorophenyl)nortropane ([18F]FECNT) is a radiotracer for positron emission tomography (PET) used to trace the location and binding potential (BP) of the dopamine transporter (DAT). We tested the hypothesis that adrenergic receptor agonists increase the BP of [18F]FECNT for the DAT. PROCEDURES: Anesthetized monkeys were scanned twice to determine the ligand BP at baseline and during administration of phenylephrine (3–6 μg/kg/min) or norepinephrine (0.5–1 μg/kg/min). Standard immunohistochemistry and immunoblot analyses were performed in rats to determine if the quantity of DAT changed with phenylephrine. [18F]FECNT uptake in human embryonic kidney (HEK) cells, stably transfected with DAT cDNA, was measured by gamma scintillation counting during phenylephrine. RESULTS: The PET measured BP of [18F]FECNT increased by 50% and 45% during the phenylephrine and norepinephrine infusion, respectively. The immunohistochemistry and immunoblot analyses did not show a difference in total DAT. CONCLUSION: Adrenergic agonists increase the BP of [18F]FECNT in monkey striatum.

Phenylephrine and norepinephrine increase dopamine transporter ligand binding in striatum.

3,6-Dioxabicyclo[3.1.0]hexane-2,4-dimethanol, C6H10O4, M(r) = 146.1, orthorhombic, P2(1)2(1)2(1), a = 7.6209 (2), b = 9.1292 (3), c = 9.6135 (5) A, V = 668.8 (1) A3, Z = 4, Dx = 1.451 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 1.15 cm-1, F(000) = 312, T = 298 K, R = 0.029 for 1280 observations with I greater than 3 sigma(I) (of 1695 unique data). The tetrahydrofuran ring has the envelope conformation, OE, with P of 94.3 degrees and tau m = 24.0 degrees. C atoms deviate from their best plane by +/- 0.0006 (1) to 0.010 (1) A, and the O atom lies 0.331 (1) A from that plane. The epoxide O atom is syn to the tetrahydrofuran O atom. Each hydroxy group is involved in intermolecular hydrogen bonding both as donor and acceptor. The two hydrogen bonds have O...O distances of 2.743 (1) and 2.729 (1) A, and angles about H of 166.3 (12) and 172 (2) degrees, respectively.

Ronald J. Voll

Papers

Characterization of the two enantiomers of anti-18F-FACPC as PET tumor agents

Syntheses and biological activities of novel 2-methoxyestradiol analogs, 2-fluoroethoxyestradiol and 2-fluoropropanoxyestradiol, and a radiosynthesis of 2-[18F]fluoroethoxyestradiol for positron emission tomography

Synthesis of a phenolic precursor and its efficient O-[18F]fluoroethylation with purified no-carrier-added [18F]2-fluoroethyl brosylate as the labeling agent.

Phenylephrine and norepinephrine increase dopamine transporter ligand binding in striatum.

Structure of 2,5:3,4-dianhydro-D-altritol.