Search results for "Radiosynthesis"
showing 10 items of 15 documents
Two-step radiosynthesis of [18F]FE-β-CIT and [18F]PR04.MZ
2013
The cocaine-derived dopamine reuptake inhibitors FE-β-CIT (8-(2-fluoroethyl)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester) (1) and PR04.MZ(8-(4-fluorobut-2-ynyl)-3-p-tolyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester) (2) were labelled with (18)F-fluorine using a two-step route. 2-[(18)F]Fluoroethyltosylate and 4-[(18)F]fluorobut-2-yne-1-yl tosylate were used as labelling reagents, respectively. Radiochemically pure (>98%) [(18)F]FE-β-CIT and [(18)F]PRD04.MZ (32-86 GBq/µmol) were obtained after a synthesis time of 100 min in about 25% non-decay-corrected overall yield.
Synthesis and radiosynthesis of N5-[18F]fluoroethyl-Pirenzepine and its metabolite N5-[18F]fluoroethyl-LS 75
2009
The well established M1 selective muscarinergic antagonist Pirenzepine 11-[2-(4-methyl-piperazin-1-yl)-acetyl]-5,11-dihydro-benzo[e]pyrido[3,2-b][1,4]diazepin-6-one (1) exhibits an unusual behaviour in vivo, which cannot be explained with M1 antagonism exclusively. One of the aspects discussed is a specific interaction with poly ADP-ribose polymerase (PARP-1). 1 undergoes metabolism to form LS 75 5,11-dihydro-benzo[e]pyrido[3,2-b][1,4]diazepin-6-one (2). In order to study deviations in Pirenzepine efficacy from pure M1 binding in vivo using PET, appropriate positron emitter labelled analogues of 1 and 2 were synthesised. Non-radioactive reference compounds 3 and 4 were tested for PARP-1 inh…
PET Chemistry: Radiopharmaceuticals
2021
Although many radiolabelled compounds for PET imaging have been developed so far, only a few have reached the status of a clinically established and routinely used PET radiopharmaceutical. At the early stage of development, a reasonable medical indication is obviously fundamental for a PET radiopharmaceutical to be further considered as clinically relevant. However, besides a favourable in vivo behaviour and appropriate imaging characteristics, certain criteria have to be fulfilled, such as a fast, straightforward and reliable radiosynthesis; an assured stability of the label as well as of the compound itself and a good availability of a suitable precursor. In particular, the ease and relia…
A convenient chemo-enzymatic synthesis and 18F-labelling of both enantiomers of trans-1-toluenesulfonyloxymethyl-2-fluoromethyl-cyclopropane
2008
The present report is concerned with a stereoselective, reliable route to trans-1,2-disubstituted cyclopropanes and in particular to (S,S)-1-tosyloxymethyl-2-fluoromethyl-cyclopropane (1) and (R,R)-1-tosyloxymethyl-2-fluoromethyl-cyclopropane (ent-1) as conformationally restricted, terminally fluorinated C4-building blocks for medicinal chemistry. The enzymatic kinetic resolution based synthesis of 1 and ent-1 utilises inexpensive, commercially available starting materials. It is based on enantiomeric resolution of rac-cyclopropane carboxylic esters using esterase from Streptomyces diastatochromogenes. Both enantiomers of 1 were prepared selectively in high overall yield over nine steps, st…
Synthèse de pinces à fluorures dérivées d'aminoacides pour l'imagerie TEP
2014
This thesis project, which is part of a collaboration between the Institut de Chimie Moléculaire de l’Université de Bourgogne and the Positron Emission Tomography Research Centre, is about the synthesis of fluoride pincers derived from amino acids based on 18F-B bond construction to get a new class of PET imaging agents. First, this project concerned the design, synthesis and characterisation of new boronato and trifluoroborato phosphonium amino acid salts. Quaternisation of o-boronate phenyl phosphine with β-iodo amino esters or γ-iodo amino ester leads to the corresponding salts without racemisation and in yields up to 88%. Saponification of boronato phosphonium amino esters afford the fr…
Efficient microwave-assisted direct radiosynthesis of [(18)F]PR04.MZ and [(18)F]LBT999: selective dopamine transporter ligands for quantitative molec…
2009
Abstract PR04.MZ 8-(4-fluoro-but-2-ynyl)-3- p -tolyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester ( 1 ) and LBT999 8-(( E )-4-fluoro-but-2-enyl)-3b- p -tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid methyl ester ( 2 ) are selective dopamine reuptake inhibitors, derived from cocaine. Compounds 1 and 2 were labelled with fluorine-18 at their terminally fluorinated N-substituents employing microwave enhanced direct nucleophilic fluorination. K[ 18 F]F − Kryptofix ® 222 cryptate, tetrabutyl ammonium [ 18 F]fluoride and caesium [ 18 F]fluoride were compared as fluoride sources under conventional and microwave enhanced conditions. Fluorination yields were remarkably increased un…
Synthesis of No-Carrier-Added 4-[18F]Fluorophenol from 4-Benzyloxyphenyl-(2-thienyl)iodonium Bromide
2011
4-[(18)F]Fluorophenol is a versatile synthon for the synthesis of more complex radiopharmaceuticals bearing a 4-[(18)F]fluorophenoxy moiety. In order to prepare 4-[(18)F]fluorophenol in no-carrier-added (n.c.a.) form only a nucleophilic labelling method starting from [(18)F]fluoride is suitable. In this paper a new, two step radiosynthesis starting from 4-benzyloxyphenyl-(2-thienyl)iodonium bromide and [(18)F]fluoride with subsequent deprotection is described, yielding n.c.a. [(18)F]fluorophenol in 34 to 36% radiochemical yield.
An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY® Nickel catalyzed reductive cyclization
2015
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…
Synthesis, labelling and evaluation of hydantoin-substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of…
2011
The N-methyl- d-aspartate (NMDA) receptor as a type of ionotropic glutamatergic receptors is essential for physiological processes such as learning, memory and synaptic plasticity. A glutamate-induced overactivation of these receptors, accompanied by increased intracellular calcium concentration, causes cell injury and leads to a large number of acute or chronic neurological disorders, such as stroke, trauma, Parkinson's disease and Alzheimer's disease. In an attempt to visualise the glutamatergic neurotransmission in vivo with positron emission tomography, novel fluoroethoxy- and methoxy-substituted reference compounds based on the lead structure of a hydantoin-substituted indole-2-carboxy…
Improved radiosynthesis and preliminary in vivo evaluation of the 11C-labeled tetrazine [11C]AE-1 for pretargeted PET imaging
2019
Pretargeted nuclear imaging based on the ligation between tetrazines and nano-sized targeting agents functionalized with trans-cyclooctene (TCO) has recently been shown to improve both imaging contrast and dosimetry in nuclear imaging of nanomedicines. Herein, we describe the improved radiosynthesis of a 11 C-labeled tetrazine ([ 11 C]AE-1) and its preliminary evaluation in both mice and pigs. Pretargeted imaging in mice was carried out using both a new TCO-functionalized polyglutamic acid and a previously reported TCO-functionalized bisphosphonate system as targeting agents. Unfortunately, pretargeted imaging was not successful using these targeting agents in pair with [ 11 C]AE-1. Howeve…