Publication

Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography

Luurtsema, G., Windhorst, AD., Mooijer, MPJ., Herscheid, JDM., Lammertsma, AA. & Franssen, EJF., Dec-2002, In : JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS. 45, 14, p. 1199-1207 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Luurtsema, G., Windhorst, AD., Mooijer, MPJ., Herscheid, JDM., Lammertsma, AA., & Franssen, EJF. (2002). Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography. JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 45(14), 1199-1207. https://doi.org/10.1002/jlcr.632

Author

Luurtsema, G ; Windhorst, AD ; Mooijer, MPJ ; Herscheid, JDM ; Lammertsma, AA ; Franssen, EJF. / Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography. In: JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS. 2002 ; Vol. 45, No. 14. pp. 1199-1207.

Harvard

Luurtsema, G, Windhorst, AD, Mooijer, MPJ, Herscheid, JDM, Lammertsma, AA & Franssen, EJF 2002, 'Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography', JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, vol. 45, no. 14, pp. 1199-1207. https://doi.org/10.1002/jlcr.632

Standard

Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography. / Luurtsema, G; Windhorst, AD; Mooijer, MPJ; Herscheid, JDM; Lammertsma, AA; Franssen, EJF.

In: JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, Vol. 45, No. 14, 12.2002, p. 1199-1207.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Luurtsema G, Windhorst AD, Mooijer MPJ, Herscheid JDM, Lammertsma AA, Franssen EJF. Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography. JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS. 2002 Dec;45(14):1199-1207. https://doi.org/10.1002/jlcr.632


BibTeX

@article{3103e926de5d410785a84ef01014fb72,
title = "Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography",
abstract = "Racemic (+/-) verapamil is a well characterized substrate for P-glycoprotein (P-gp). However, the in vivo pharmacokinetics and pharmacodynamics of both enantiomers are reported to be different. In the preparation of evaluation studies of both enantiomers in animals and humans, the purpose of the present study was to optimize and automate the synthesis of (R)- and (S)[C-11]verapamil.(R)- and (S)-[C-11]verapamil were prepared from (R)- and (S)-desmethyl-verapamil, respectively, by methylation with no-carrier added [C-11]methyliodide or [C-11]methyltriflate. Different conditions of the methylation reaction were studied: reaction time, temperature, base and solvent, and chemical form of the precursor using either the hydrochloric acid salt or the free base of the starting material. After optimization, the synthesis was fully automated using home-made modules and performed according to GMP guidelines. Optimal yields of 60-70{\%} for the methylation reaction were obtained using 1.5 mg of the free base of (R)- or (S)-desmethyl-verapamil in 0.5ml of acetonitrile at 50degreesC for 5 min with [C-11]methyltriflate as methylating agent. Under the same reaction conditions, but with a reaction temperature of 100degreesC, the radiochemical yield starting with [C-11]methyliodide as methylation reagent was 40{\%}. The specific activity of (R)- and (S)[C-11]verapamil was > 20 GBq/mumol and the radiochemical purity was > 99{\%} for both methods. The total synthesis time was 45 min. The automated high yield synthesis of (R)- and (S)-[C-11]verapamil provides the means for evaluating both enantiomers as in vivo tracers of P-gp function. Copyright (C) 2002 John Wiley Sons, Ltd.",
keywords = "[C-11]methyliodide, [C-11]methyltriflate, enantiomers, P-gp, verapamil, C-11 METHYL TRIFLATE, STEREOSELECTIVE 1ST-PASS METABOLISM, MULTIDRUG-RESISTANCE, IN-VIVO, VERAPAMIL, PET, TRANSPORT, COMPLEXES, TUMORS, DRUGS",
author = "G Luurtsema and AD Windhorst and MPJ Mooijer and JDM Herscheid and AA Lammertsma and EJF Franssen",
year = "2002",
month = "12",
doi = "10.1002/jlcr.632",
language = "English",
volume = "45",
pages = "1199--1207",
journal = "JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS",
issn = "0362-4803",
publisher = "Wiley",
number = "14",

}

RIS

TY - JOUR

T1 - Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography

AU - Luurtsema, G

AU - Windhorst, AD

AU - Mooijer, MPJ

AU - Herscheid, JDM

AU - Lammertsma, AA

AU - Franssen, EJF

PY - 2002/12

Y1 - 2002/12

N2 - Racemic (+/-) verapamil is a well characterized substrate for P-glycoprotein (P-gp). However, the in vivo pharmacokinetics and pharmacodynamics of both enantiomers are reported to be different. In the preparation of evaluation studies of both enantiomers in animals and humans, the purpose of the present study was to optimize and automate the synthesis of (R)- and (S)[C-11]verapamil.(R)- and (S)-[C-11]verapamil were prepared from (R)- and (S)-desmethyl-verapamil, respectively, by methylation with no-carrier added [C-11]methyliodide or [C-11]methyltriflate. Different conditions of the methylation reaction were studied: reaction time, temperature, base and solvent, and chemical form of the precursor using either the hydrochloric acid salt or the free base of the starting material. After optimization, the synthesis was fully automated using home-made modules and performed according to GMP guidelines. Optimal yields of 60-70% for the methylation reaction were obtained using 1.5 mg of the free base of (R)- or (S)-desmethyl-verapamil in 0.5ml of acetonitrile at 50degreesC for 5 min with [C-11]methyltriflate as methylating agent. Under the same reaction conditions, but with a reaction temperature of 100degreesC, the radiochemical yield starting with [C-11]methyliodide as methylation reagent was 40%. The specific activity of (R)- and (S)[C-11]verapamil was > 20 GBq/mumol and the radiochemical purity was > 99% for both methods. The total synthesis time was 45 min. The automated high yield synthesis of (R)- and (S)-[C-11]verapamil provides the means for evaluating both enantiomers as in vivo tracers of P-gp function. Copyright (C) 2002 John Wiley Sons, Ltd.

AB - Racemic (+/-) verapamil is a well characterized substrate for P-glycoprotein (P-gp). However, the in vivo pharmacokinetics and pharmacodynamics of both enantiomers are reported to be different. In the preparation of evaluation studies of both enantiomers in animals and humans, the purpose of the present study was to optimize and automate the synthesis of (R)- and (S)[C-11]verapamil.(R)- and (S)-[C-11]verapamil were prepared from (R)- and (S)-desmethyl-verapamil, respectively, by methylation with no-carrier added [C-11]methyliodide or [C-11]methyltriflate. Different conditions of the methylation reaction were studied: reaction time, temperature, base and solvent, and chemical form of the precursor using either the hydrochloric acid salt or the free base of the starting material. After optimization, the synthesis was fully automated using home-made modules and performed according to GMP guidelines. Optimal yields of 60-70% for the methylation reaction were obtained using 1.5 mg of the free base of (R)- or (S)-desmethyl-verapamil in 0.5ml of acetonitrile at 50degreesC for 5 min with [C-11]methyltriflate as methylating agent. Under the same reaction conditions, but with a reaction temperature of 100degreesC, the radiochemical yield starting with [C-11]methyliodide as methylation reagent was 40%. The specific activity of (R)- and (S)[C-11]verapamil was > 20 GBq/mumol and the radiochemical purity was > 99% for both methods. The total synthesis time was 45 min. The automated high yield synthesis of (R)- and (S)-[C-11]verapamil provides the means for evaluating both enantiomers as in vivo tracers of P-gp function. Copyright (C) 2002 John Wiley Sons, Ltd.

KW - [C-11]methyliodide

KW - [C-11]methyltriflate

KW - enantiomers

KW - P-gp

KW - verapamil

KW - C-11 METHYL TRIFLATE

KW - STEREOSELECTIVE 1ST-PASS METABOLISM

KW - MULTIDRUG-RESISTANCE

KW - IN-VIVO

KW - VERAPAMIL

KW - PET

KW - TRANSPORT

KW - COMPLEXES

KW - TUMORS

KW - DRUGS

U2 - 10.1002/jlcr.632

DO - 10.1002/jlcr.632

M3 - Article

VL - 45

SP - 1199

EP - 1207

JO - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS

JF - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS

SN - 0362-4803

IS - 14

ER -

ID: 22571200