The Service Hospitalier Frédéric Joliot – contributions to PET chemistry over the years

Roeda, Dirk; Kühnast, Bertrand; Hammadi, Akli; Dollé, Frédéric

doi:10.1002/jlcr.1420

Cited by 9 publications

(5 citation statements)

References 201 publications

(56 reference statements)

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“…Previously, it has been shown that rhodium-mediated reactions with 11 C]CO, forming ureas, are rapid and provide high yield [23-25]. Therefore, in the present, study 11 C]CO was used to synthesize 11 C]phenytoin by rhodium-mediated carbonylation with the aim of improving both specific activity and radiochemical yield of 11 C]phenytoin compared with an earlier method based on 11 C]COCl 2 [26], which resulted in low specific activity of the product following a rather tedious radiochemistry [26,27]. The purpose of the present study was to synthesize 11 C]phenytoin by carbonylation and to assess its characteristics as a P-gp substrate in rats in vivo .…”

Section: Introductionmentioning

confidence: 99%

[11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats

et al. 2012

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BackgroundAt present, several positron emission tomography (PET) tracers are in use for imaging P-glycoprotein (P-gp) function in man. At baseline, substrate tracers such as R-[11C]verapamil display low brain concentrations with a distribution volume of around 1. [11C]phenytoin is supposed to be a weaker P-gp substrate, which may lead to higher brain concentrations at baseline. This could facilitate assessment of P-gp function when P-gp is upregulated. The purpose of this study was to synthesize [11C]phenytoin and to characterize its properties as a P-gp tracer.Methods[11C]CO was used to synthesize [11C]phenytoin by rhodium-mediated carbonylation. Metabolism and, using PET, brain pharmacokinetics of [11C]phenytoin were studied in rats. Effects of P-gp function on [11C]phenytoin uptake were assessed using predosing with tariquidar.Results[11C]phenytoin was synthesized via [11C]CO in an overall decay-corrected yield of 22 ± 4%. At 45 min after administration, 19% and 83% of radioactivity represented intact [11C]phenytoin in the plasma and brain, respectively. Compared with baseline, tariquidar predosing resulted in a 45% increase in the cerebral distribution volume of [11C]phenytoin.ConclusionsUsing [11C]CO, the radiosynthesis of [11C]phenytoin could be improved. [11C]phenytoin appeared to be a rather weak P-gp substrate.

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Section: Introductionmentioning

confidence: 99%

[11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats

et al. 2012

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“…The use of the methylation reagent [ 11 C]methyl triflate41–44 was privileged for the labeling at the 5‐methylpyridazino[4,5‐ b ]indole moiety (leading to compound 1a ), whereas [ 11 C]methyl iodide45 was preferred for the labeling at the N,N ‐dimethylacetamide function (leading to compound 1b ), a choice based on literature reports as well as on our own experience with similar structures 4, 25, 46. The nor ‐derivatives needed as precursors for labeling as well as SSR180575 itself needed as a reference were synthesized at Sanofi‐Aventis 47…”

Section: Resultsmentioning

confidence: 99%

Radiosynthesis of 7‐chloro‐N,N‐dimethyl‐5‐[¹¹C]methyl‐4‐oxo‐3‐phenyl‐3,5‐dihydro‐4H‐pyridazino[4,5‐b]indole‐1‐acetamide, [¹¹C]SSR180575, a novel radioligand for imaging the TSPO (peripheral benzodiazepine receptor) with PET

Thominiaux

Damont

Kühnast

et al. 2010

Labelled Comp Radiopharmac

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SSR180575 (7‐chloro‐N,N,5‐trimethyl‐4‐oxo‐3‐phenyl‐3,5‐dihydro‐4H‐pyridazino[4,5‐b]indole‐1‐acetamide) is the lead compound of an original pyridazinoindole series of potent and highly selective TSPO (peripheral benzodiazepine receptor) ligands. Isotopic labeling of SSR180575 with the short‐lived positron‐emitter carbon‐11 (T1/2: 20.38 min) at its 5‐methylpyridazino[4,5‐b]indole moiety as well as at its N,N‐dimethylacetamide function by methylation of the corresponding nor‐analogues was investigated. Best results in terms of radiochemical yields and purities were obtained for the preparation of [indole‐N‐methyl‐11C]SSR180575, where routine production batches of 4.5–5.0 GBq of radiochemically pure (>99%) i.v. injectable solutions (specific radioactivities: 50–90 GBq/µmol) could be prepared within a total synthesis time of 25 min (HPLC purification included) starting from a 55 GBq [11C]CO2 cyclotron production batch (non‐decay‐corrected overall radiochemical yields: 8–9%). The process comprises (1) trapping at −10°C of [11C]methyl triflate in DMF (300 µl) containing 0.2–0.3 mg of the indole precursor for labeling and 4 mg of K2CO3 (excess); (2) heating at 120°C for 3 min; (3) dilution of the residue with 0.5 ml of the HPLC mobile phase and (4) purification using semi‐preparative reversed‐phase HPLC (Zorbax® SB‐C‐18). In vivo pharmacological properties of [indole‐N‐methyl‐11C]SSR180575 as a candidate for imaging neuroinflammation with positron emission tomography are currently evaluated. Copyright © 2010 John Wiley & Sons, Ltd.

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“…The successful use of carbon‐11 in the labelling of an impressive variety of chemical structures is undoubtedly related to the exhaustive development of the so‐called secondary precursors . These labelled synthons, usually single‐carbon reactive molecules, are prepared from a primary precursor ([ 11 C]CO 2 or [ 11 C]CH 4 ), often by ‘on‐line’ or one‐pot procedures and are used as building blocks for the labelling of different chemical functions.…”

Section: Introductionmentioning

confidence: 99%

The potential of carbon‐11 and fluorine‐18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa

Damont

Roeda

Dollé

2013

Labelled Comp Radiopharmac

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The TSPO (translocator protein), also known as the peripheral benzodiazepine receptor, is upregulated in the brain of subjects suffering from neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. Moreover, this overexpression has been proved to be linked to microglia activation making thus the TSPO a marker of choice of neuroinflammatory processes and therefore a potential target for the development of radioligands for positron emission tomography imaging. The discovery of selective TSPO ligands and their labelling with the short-lived positron-emitter isotopes carbon-11 and fluorine-18 emerged in the mid-1980s with the preparation of the 3-isoquinolinecarboxamide [(11) C]PK11195. To date, an impressive number of promising compounds-[(11) C]PK11195-challengers-have been developed; some radioligands-for example, [(11) C]PBR28, [(11) C]DPA-713, [(18) F]FEDAA1106 and [(18) F]DPA-714-are currently used in clinical trials. As illustrated in this review, the methodologies applied for the preparation of these compounds remain mainly [(11) C]methylations using [(11) C]MeI or [(11) C]MeOTf and SN 2-type nucleophilic aliphatic [(18) F]fluorinations-two processes illustrating the state-of-the-art arsenal of reactions that involves these two short-lived radioisotopes-but alternative processes, such as [(11) C]carbonylations using [(11) C]CO and [(11) C]COCl2 as well as SN Ar-type nucleophilic [(18) F]fluorinations, have also been reported and as such, reviewed herein.

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The Service Hospitalier Frédéric Joliot – contributions to PET chemistry over the years

Cited by 9 publications

References 201 publications

[11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats

[11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats

Radiosynthesis of 7‐chloro‐N,N‐dimethyl‐5‐[¹¹C]methyl‐4‐oxo‐3‐phenyl‐3,5‐dihydro‐4H‐pyridazino[4,5‐b]indole‐1‐acetamide, [¹¹C]SSR180575, a novel radioligand for imaging the TSPO (peripheral benzodiazepine receptor) with PET

The potential of carbon‐11 and fluorine‐18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa

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The Service Hospitalier Frédéric Joliot – contributions to PET chemistry over the years

Cited by 9 publications

References 201 publications

[11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats

[11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats

Radiosynthesis of 7‐chloro‐N,N‐dimethyl‐5‐[11C]methyl‐4‐oxo‐3‐phenyl‐3,5‐dihydro‐4H‐pyridazino[4,5‐b]indole‐1‐acetamide, [11C]SSR180575, a novel radioligand for imaging the TSPO (peripheral benzodiazepine receptor) with PET

The potential of carbon‐11 and fluorine‐18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa

Contact Info

Product

Resources

About

Radiosynthesis of 7‐chloro‐N,N‐dimethyl‐5‐[¹¹C]methyl‐4‐oxo‐3‐phenyl‐3,5‐dihydro‐4H‐pyridazino[4,5‐b]indole‐1‐acetamide, [¹¹C]SSR180575, a novel radioligand for imaging the TSPO (peripheral benzodiazepine receptor) with PET