Dynamic Precision Phenotyping Reveals Mechanism of Crop Tolerance to Root Herbivory.

The western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte) is a major pest of maize (Zea mays) that is well adapted to most crop management strategies. Breeding for tolerance is a promising alternative to combat WCR but is currently constrained by a lack of physiological understanding and phenotyping tools. We developed dynamic precision phenotyping approaches using 11C with positron emission tomography, root autoradiography, and radiometabolite flux analysis to understand maize tolerance to WCR. Our results reveal that WCR attack induces specific patterns of lateral root growth that are associated with a shift in auxin biosynthesis from indole-3-pyruvic acid to indole-3-aceton…

[(11)C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient (11)C-O-methylation and initial small animal PET studies.

PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [{sup 11}C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [{sup 11}C]MeI mediated synthesis of [{sup 11}C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb{sub 2}CO{sub 3} in DMF in up to 95 {+-} 5% labelling yield. A preliminary {mu}PET-experim…

Synthesis of l -[4-11 C]Asparagine by Ring-Opening Nucleophilic 11 C-Cyanation Reaction of a Chiral Cyclic Sulfamidate Precursor

The development of a convenient and rapid method to synthesize radiolabeled, enantiomerically pure amino acids (AAs) as potential positron emission tomography (PET) imaging agents for mapping various biochemical transformations in living organisms remains a challenge. This is especially true for the synthesis of carbon-11-labeled AAs given the short half-life of carbon-11 (11 C, t1/2 =20.4 min). A facile synthetic pathway to prepare enantiomerically pure 11 C-labeled l-asparagine was developed using a partially protected serine as a starting material with a four-step transformation providing a chiral five-membered cyclic sulfamidate as the radiolabeling precursor. Its structure and absolute…

An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY® Nickel catalyzed reductive cyclization

A rapid method for the synthesis of carbon-11 radiolabeled indole was developed using a sub-nanomolar quantity of no-carrier-added [(11)C]cyanide as radio-precursor. Based upon a reported synthesis of 2-(2-nitrophenyl)acetonitrile (), a highly reactive substrate 2-nitrobenzyl bromide () was evaluated for nucleophilic [(11)C]cyanation. Additionally, related reaction conditions were explored with the goal of obtaining of highly reactive 2-(2-nitrophenyl)-[1-(11)C]acetonitrile () while inhibiting its rapid conversion to 2,3-bis(2-nitrophenyl)-[1-(11)C]propanenitrile (). Next, a RANEY® Nickel catalyzed reductive cyclization method was utilized for synthesizing the desired [2-(11)C]indole with h…

PET Studies of d-Methamphetamine Pharmacokinetics in Primates: Comparison with l-Methamphetamine and (—)-Cocaine

The methamphetamine molecule has a chiral center and exists as 2 enantiomers, d-methamphetamine (the more active enantiomer) and l-methamphetamine (the less active enantiomer). d-Methamphetamine is associated with more intense stimulant effects and higher abuse liability. The objective of this study was to measure the pharmacokinetics of d-methamphetamine for comparison with both l-methamphetamine and (-)-cocaine in the baboon brain and peripheral organs and to assess the saturability and pharmacologic specificity of binding.d- and l-methamphetamine and (-)-cocaine were labeled with (11)C via alkylation of the norprecursors with (11)C-methyl iodide using literature methods. Six different ba…

Evaluation of [11C]Metergoline as a PET Radiotracer for 5HTR in Nonhuman Primates

Metergoline, a serotonin receptor antagonist, was labeled with carbon-11 in order to evaluate its pharmacokinetics and distribution in non-human primates using positron emission tomography. [{sup 11}C]Metergoline had moderate brain uptake and exhibited heterogeneous specific binding, which was blocked by pretreatment with metergoline and altanserin throughout the cortex. Non-specific binding and insensitivity to changes in synaptic serotonin limit its potential as a PET radiotracer. However, the characterization of [{sup 11}C]metergoline pharmacokinetics and binding in the brain and peripheral organs using PET improves our understanding of metergoline drug pharmacology.

Reinvestigation of the synthesis and evaluation of [N-methyl-11C]vorozole, a radiotracer targeting cytochrome P450 aromatase

Abstract Introduction We reinvestigated the synthesis of [ N -methyl- 11 C]vorozole, a radiotracer for aromatase, and discovered the presence of an N -methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [ N -methyl- 11 C]vorozole. Methods Norvorozole was alkylated with [ 11 C]methyl iodide as previously described and also with unlabeled methyl iodide. A high-performance liquid chromatography (HPLC) method was developed to separate the regioisomers. Nuclear magnetic resonance (NMR) spectroscopy ( 13 C and 2D-nuclear Overhauser effect spectroscopy NMR) was used to identify and assign s…

Automated GMP production of [11C]PR04.MZ via the captive solvent method and PET studies in non-human primates: A promising tracer for extrastriatal DAT imaging

Radiosynthesis of 3-indolyl[1-11C]acetic acid for phyto-PET-imaging: An improved production procedure and formulation method

Abstract An improved production procedure and formulation method for the carbon-11 radiolabeled phytohormone, 3-indolyl-[l- 11 C]acetic acid ([ 11 C]IAA), was developed by modifying selected original reaction parameters. This updated procedure both doubled the yield (from 25.9±6.7% ( n =12) to 61.0±0.3% ( n =10)) and increased the concentration (0.2–0.4 GBq/0.15–0.3 mL), enabling us to provide the radiotracer [ 11 C]IAA suitable for in vivo phyto-PET-imaging studies. The specific activity was improved by more than a factor of three (26.7±5.6 GBq/µmol to 82.5±36.1 GBq/µmol). The total synthesis time for both production and formulation was 81.8±3.0 min ( n =10). In addition, a streamlined sem…

CCDC 1415388: Experimental Crystal Structure Determination

Related Article: Youwen Xu, Aylin Sibel Cankaya, Ruma Hoque, So Jeong Lee, Colleen Shea, Lena Kersting, Michael Schueller, Joanna S. Fowler, David Szalda, David Alexoff, Barbara Riehl, Tassilo Gleede, Richard A. Ferrieri, Wenchao Qu|2018|Chem.-Eur.J.|24|6848|doi:10.1002/chem.201801029