Asymmetric synthesis of a precursor for the automated radiosynthesis of as a preferred radioligand for β-adrenergic receptors

Brady, F.; Luthra, Sajinder K.; Tochon-Danguy, Henri-J.; Steel, Colin; Waters, S.L.; Kensett, M.J.; Landais, P.; Shah, Farah; Jaeggi, Knut A.; Drake, Alex F.; Clark, John C.; Pike, Victor W.

doi:10.1016/0883-2889(91)90032-v

Cited by 58 publications

(36 citation statements)

References 15 publications

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“…Recently, the same group has improved the in vivo quantification of cardiac β-ARs in mini pigs using the more potent enantiomer (S)-[ 11 C]CGP 12177 (1) [68]. However, for the first time the asymmetric synthesis of (S)-[ 11 C]CGP 12177 (1) was almost simultaneously reported by Brady et al [69] and Hammadi et al [74]. Since then preclinical studies had suggested the (S)-enantiomer as promising nonsubtype-selective β-AR radioligand for PET imaging with high myocardial uptake [70] whereas radioactive metabolites occur to a minor extent [71].…”

Section: [ 11 C]phosgene As Radiolabeling Synthonmentioning

confidence: 90%

“…The radiosynthetic procedures for the preparation of the racemate [73] or the (S)-enantiomer [69,74] make use of the radiochemical synthon [ 11 C]phosgene [75,76] as radioactive precursor to label the radioligand at ambient temperatures at the C-2-carbonyl position of the benzimidazolone by condensation with the non-radioactive diamino precursor 1-(2,3-Diaminophenoxy)-3-(N-tert-butylamino)propan-2-ol [77] (Fig. 7).…”

Section: [ 11 C]phosgene As Radiolabeling Synthonmentioning

confidence: 99%

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Non-Invasive Molecular Imaging of β-Adrenoceptors In Vivo: Perspectives for PET-Radioligands

Kopka¹,

Law²,

Breyholz³

et al. 2005

CMC

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Recently, the spectrum of molecular imaging devices such as positron emission tomography (PET) was further expanded by the now clinically available combined imaging modalities such as PET-CT and the preclinically used small animal PET scanners. These are powerful tools that can bridge the gap between preclinical and clinical evaluation studies of new radiotracers for molecular imaging of healthy and diseased states in vivo. The beta-adrenoceptor (beta-AR) radioligands discussed in this review represent a class of molecular probes for the non-invasive in vivo assessment of beta-AR density eg. in the heart with PET. The beta-AR radioligands (S)-[11C]CGP 12177 (1) or (S)-[11C]CGP 12388 (2) are currently investigated in clinical studies with PET. Additionally, subtype-selective beta1-AR radioligands are used in preclinical research which show potential for the diagnostics of the "beta1-AR organ" as such the heart can be defined. Non-invasive quantification of beta-ARs could facilitate the accurate choice and control of therapeutic interventions. Here we summarize the state-of-the-art of the radiochemistry of radioactive beta-AR radioligands.

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Section: [ 11 C]phosgene As Radiolabeling Synthonmentioning

confidence: 90%

Section: [ 11 C]phosgene As Radiolabeling Synthonmentioning

confidence: 99%

Non-Invasive Molecular Imaging of β-Adrenoceptors In Vivo: Perspectives for PET-Radioligands

Kopka¹,

Law²,

Breyholz³

et al. 2005

CMC

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“…54 The importance of chirality for improving the in vivo efficacy of PET radiotracers was already evident and the significant success in organic chemistry contributed to the development of improved homochiral radioligands and S-[ 11 C]CGP 12177 was an example. Subsequent improvements to the radiosynthesis of [ 11 C]phosgene were carried out using liquid ammonia for the synthesis permitting more reliable production of and applying it to the synthesis of [ (Figure 7).…”

Section: Carbon-11mentioning

confidence: 99%

Building on a 50‐year legacy of the MRC Cyclotron Unit: the Hammersmith radiochemistry pioneering journey

Brady¹,

Clark²,

Luthra³

2007

Labelled Comp Radiopharmac

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The Medical Research Council Cyclotron Unit (MRC CU) situated at Hammersmith Hospital, London, is widely recognised for its pioneering developments in radiochemistry. The MRC CU became one of the largest and most comprehensive PET centres in the world. More recently, under the umbrella of a public/private partnership between the MRC and Amersham Health (now part of GE Healthcare) this centre has continued to advance PET research.This article reviews the 50-year history of radiochemistry development and application for medical research at Hammersmith.

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“…9 Studies evaluating the accuracy and reproducibility of 11 C-CGP-12177 and PET for the quantification of ␤-adrenergic receptor density showed excellent results. 16,17 After initial rectilinear, transmission, and blood volume ([ 15 O]CO) scanning, measurement of myocardial ␤-adrenergic receptor density was performed according to a modification of the double-injection method previously reported in detail.…”

Section: Postsynaptic ␤-Adrenergic Receptor Densitymentioning

confidence: 99%

Abnormalities of Cardiac Sympathetic Innervation in Arrhythmogenic Right Ventricular Cardiomyopathy

et al. 2000

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Background-The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by 123 I-MIBG-single-photon emission computed tomography. Methods and Results-This study investigated neuronal reuptake of norepinephrine (uptake-1) and ␤-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V d ) of [ 11 C]hydroxyephedrine ( 11 C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B max ) of ). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects.Conclusions-The findings demonstrate a significant reduction of myocardial ␤-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine reuptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management. (Circulation. 2000;101:1552-1558.)

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Asymmetric synthesis of a precursor for the automated radiosynthesis of as a preferred radioligand for β-adrenergic receptors

Cited by 58 publications

References 15 publications

Non-Invasive Molecular Imaging of β-Adrenoceptors In Vivo: Perspectives for PET-Radioligands

Non-Invasive Molecular Imaging of β-Adrenoceptors In Vivo: Perspectives for PET-Radioligands

Building on a 50‐year legacy of the MRC Cyclotron Unit: the Hammersmith radiochemistry pioneering journey

Abnormalities of Cardiac Sympathetic Innervation in Arrhythmogenic Right Ventricular Cardiomyopathy

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Asymmetric synthesis of a precursor for the automated radiosynthesis of as a preferred radioligand for β-adrenergic receptors

Cited by 58 publications

References 15 publications

Non-Invasive Molecular Imaging of &#946;-Adrenoceptors In Vivo: Perspectives for PET-Radioligands

Non-Invasive Molecular Imaging of &#946;-Adrenoceptors In Vivo: Perspectives for PET-Radioligands

Building on a 50‐year legacy of the MRC Cyclotron Unit: the Hammersmith radiochemistry pioneering journey

Abnormalities of Cardiac Sympathetic Innervation in Arrhythmogenic Right Ventricular Cardiomyopathy

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Non-Invasive Molecular Imaging of β-Adrenoceptors In Vivo: Perspectives for PET-Radioligands

Non-Invasive Molecular Imaging of β-Adrenoceptors In Vivo: Perspectives for PET-Radioligands