Publication

[18F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors

Mirfeizi, L., Rybczynska, A. A., Waarde, A. V., Campbell-Verduyn, L., Feringa, B., Dierckx, R. A. J. O. & Elsinga, P., Feb-2014, In : Nuclear Medicine and Biology. 41, 2, p. 203-209 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Mirfeizi, L., Rybczynska, A. A., Waarde, A. V., Campbell-Verduyn, L., Feringa, B., Dierckx, R. A. J. O., & Elsinga, P. (2014). [18F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors. Nuclear Medicine and Biology, 41(2), 203-209. https://doi.org/10.1016/j.nucmedbio.2013.10.011

Author

Mirfeizi, Leila ; Rybczynska, Anna A. ; Waarde, Aren van ; Campbell-Verduyn, Lachlan ; Feringa, Bernard ; Dierckx, Rudi A.J.O. ; Elsinga, Philippus. / [18F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors. In: Nuclear Medicine and Biology. 2014 ; Vol. 41, No. 2. pp. 203-209.

Harvard

Mirfeizi, L, Rybczynska, AA, Waarde, AV, Campbell-Verduyn, L, Feringa, B, Dierckx, RAJO & Elsinga, P 2014, '[18F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors', Nuclear Medicine and Biology, vol. 41, no. 2, pp. 203-209. https://doi.org/10.1016/j.nucmedbio.2013.10.011

Standard

[18F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors. / Mirfeizi, Leila; Rybczynska, Anna A.; Waarde, Aren van; Campbell-Verduyn, Lachlan; Feringa, Bernard; Dierckx, Rudi A.J.O.; Elsinga, Philippus.

In: Nuclear Medicine and Biology, Vol. 41, No. 2, 02.2014, p. 203-209.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Mirfeizi L, Rybczynska AA, Waarde AV, Campbell-Verduyn L, Feringa B, Dierckx RAJO et al. [18F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors. Nuclear Medicine and Biology. 2014 Feb;41(2):203-209. https://doi.org/10.1016/j.nucmedbio.2013.10.011


BibTeX

@article{7e99dcf656ec48a6a6b29bef58d416b3,
title = "[18F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors",
abstract = "Cerebral β‐adrenergic receptors (β‐ARs) play important roles in normal brain and changes of β-AR expression are associated with several neuropsychiatric illnesses. Given the high density of β‐AR in several brain regions, quantification of β‐AR levels using PET is feasible. However, there is a lack of radiotracers with suitable biological properties and meeting safety requirements for use in humans. We developed a PET tracer for β‐AR by 18F‐fluorination of 1-((9H-carbazol-4-yl)oxy)-3-4(4-((2-(2-(fluoromethoxy)-ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol (18F-FPTC). Methods: [18F] FPTC was synthesized by Cu(I)-catalyzed alkyne-azide cycloaddition. First, 18F‐PEGylated alkyne was prepared by 18F‐fluorination of the corresponding tosylate. Next 18F‐PEGylated alkyne was reacted with an azidoalcohol derivative of 4‐hydroxycarbazol in the presence of the phosphoramidite Monophos as a ligand and Cu(I) as a catalyst. After purification with radio‐HPLC, the binding properties of [18F FPTC were tested in β‐AR‐expressing C6‐glioma cells in vitro and in Wistar rats in vivo using microPET. Results: The radiochemical yield of 18F‐PEGylated alkyne was 74{\%}–89{\%}. The click reaction to prepare [18F]FPTC proceeded in 10 min with a conversion efficiency of 96{\%}. The total synthesis time was 55 min from the end of bombardment. Specific activities were > 120 GBq/μmol. Propranolol strongly and dose-dependently inhibited the binding of both [125I]-ICYP and [18F]FPTC to C6 glioma cells, with IC50 values in the 50–60 nM range. However, although both FPTC and propranolol inhibited cellular [125I]ICYP binding, FPTC decreased [125I]ICYP uptake by only 25{\%}, whereas propranolol reduced it by 83{\%}. [18F]FPTC has the appropriate lipophilicity to penetrate the blood brain barrier (logP + 2.48). The brain uptake reached a maximum within 2 min after injection of 20–25 MBq [18F]FPTC. SUV values ranged from 0.4 to 0.6 and were not reduced by propranolol. Cerebral distribution volume of the tracer (calculated from a Logan plot) was increased rather than decreased after propranolol treatment. Conclusion: ‘Click chemistry’ was successfully applied to the synthesis of [18F]FPTC resulting in high radiochemical yields. [18F]FPTC showed specific binding in vitro, but not in vivo. Based on the logP value and its ability to block [125I]ICYP binding to C6 cells, FPTC may be a lead to suitable cerebral β-AR ligands.",
keywords = "Click chemistry, [(18) F]FPTC, beta-AR, BETA-2-ADRENERGIC RECEPTORS, P-GLYCOPROTEIN, BRAIN, BINDING, ANTAGONIST, EXPRESSION, CARAZOLOL, DRUGS, RATS",
author = "Leila Mirfeizi and Rybczynska, {Anna A.} and Waarde, {Aren van} and Lachlan Campbell-Verduyn and Bernard Feringa and Dierckx, {Rudi A.J.O.} and Philippus Elsinga",
note = "Relation: https://www.rug.nl/research/stratingh/ date_submitted:2014 Rights: University of Groningen, Stratingh Institute for Chemistry",
year = "2014",
month = "2",
doi = "10.1016/j.nucmedbio.2013.10.011",
language = "English",
volume = "41",
pages = "203--209",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "ELSEVIER SCIENCE INC",
number = "2",

}

RIS

TY - JOUR

T1 - [18F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors

AU - Mirfeizi, Leila

AU - Rybczynska, Anna A.

AU - Waarde, Aren van

AU - Campbell-Verduyn, Lachlan

AU - Feringa, Bernard

AU - Dierckx, Rudi A.J.O.

AU - Elsinga, Philippus

N1 - Relation: https://www.rug.nl/research/stratingh/ date_submitted:2014 Rights: University of Groningen, Stratingh Institute for Chemistry

PY - 2014/2

Y1 - 2014/2

N2 - Cerebral β‐adrenergic receptors (β‐ARs) play important roles in normal brain and changes of β-AR expression are associated with several neuropsychiatric illnesses. Given the high density of β‐AR in several brain regions, quantification of β‐AR levels using PET is feasible. However, there is a lack of radiotracers with suitable biological properties and meeting safety requirements for use in humans. We developed a PET tracer for β‐AR by 18F‐fluorination of 1-((9H-carbazol-4-yl)oxy)-3-4(4-((2-(2-(fluoromethoxy)-ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol (18F-FPTC). Methods: [18F] FPTC was synthesized by Cu(I)-catalyzed alkyne-azide cycloaddition. First, 18F‐PEGylated alkyne was prepared by 18F‐fluorination of the corresponding tosylate. Next 18F‐PEGylated alkyne was reacted with an azidoalcohol derivative of 4‐hydroxycarbazol in the presence of the phosphoramidite Monophos as a ligand and Cu(I) as a catalyst. After purification with radio‐HPLC, the binding properties of [18F FPTC were tested in β‐AR‐expressing C6‐glioma cells in vitro and in Wistar rats in vivo using microPET. Results: The radiochemical yield of 18F‐PEGylated alkyne was 74%–89%. The click reaction to prepare [18F]FPTC proceeded in 10 min with a conversion efficiency of 96%. The total synthesis time was 55 min from the end of bombardment. Specific activities were > 120 GBq/μmol. Propranolol strongly and dose-dependently inhibited the binding of both [125I]-ICYP and [18F]FPTC to C6 glioma cells, with IC50 values in the 50–60 nM range. However, although both FPTC and propranolol inhibited cellular [125I]ICYP binding, FPTC decreased [125I]ICYP uptake by only 25%, whereas propranolol reduced it by 83%. [18F]FPTC has the appropriate lipophilicity to penetrate the blood brain barrier (logP + 2.48). The brain uptake reached a maximum within 2 min after injection of 20–25 MBq [18F]FPTC. SUV values ranged from 0.4 to 0.6 and were not reduced by propranolol. Cerebral distribution volume of the tracer (calculated from a Logan plot) was increased rather than decreased after propranolol treatment. Conclusion: ‘Click chemistry’ was successfully applied to the synthesis of [18F]FPTC resulting in high radiochemical yields. [18F]FPTC showed specific binding in vitro, but not in vivo. Based on the logP value and its ability to block [125I]ICYP binding to C6 cells, FPTC may be a lead to suitable cerebral β-AR ligands.

AB - Cerebral β‐adrenergic receptors (β‐ARs) play important roles in normal brain and changes of β-AR expression are associated with several neuropsychiatric illnesses. Given the high density of β‐AR in several brain regions, quantification of β‐AR levels using PET is feasible. However, there is a lack of radiotracers with suitable biological properties and meeting safety requirements for use in humans. We developed a PET tracer for β‐AR by 18F‐fluorination of 1-((9H-carbazol-4-yl)oxy)-3-4(4-((2-(2-(fluoromethoxy)-ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol (18F-FPTC). Methods: [18F] FPTC was synthesized by Cu(I)-catalyzed alkyne-azide cycloaddition. First, 18F‐PEGylated alkyne was prepared by 18F‐fluorination of the corresponding tosylate. Next 18F‐PEGylated alkyne was reacted with an azidoalcohol derivative of 4‐hydroxycarbazol in the presence of the phosphoramidite Monophos as a ligand and Cu(I) as a catalyst. After purification with radio‐HPLC, the binding properties of [18F FPTC were tested in β‐AR‐expressing C6‐glioma cells in vitro and in Wistar rats in vivo using microPET. Results: The radiochemical yield of 18F‐PEGylated alkyne was 74%–89%. The click reaction to prepare [18F]FPTC proceeded in 10 min with a conversion efficiency of 96%. The total synthesis time was 55 min from the end of bombardment. Specific activities were > 120 GBq/μmol. Propranolol strongly and dose-dependently inhibited the binding of both [125I]-ICYP and [18F]FPTC to C6 glioma cells, with IC50 values in the 50–60 nM range. However, although both FPTC and propranolol inhibited cellular [125I]ICYP binding, FPTC decreased [125I]ICYP uptake by only 25%, whereas propranolol reduced it by 83%. [18F]FPTC has the appropriate lipophilicity to penetrate the blood brain barrier (logP + 2.48). The brain uptake reached a maximum within 2 min after injection of 20–25 MBq [18F]FPTC. SUV values ranged from 0.4 to 0.6 and were not reduced by propranolol. Cerebral distribution volume of the tracer (calculated from a Logan plot) was increased rather than decreased after propranolol treatment. Conclusion: ‘Click chemistry’ was successfully applied to the synthesis of [18F]FPTC resulting in high radiochemical yields. [18F]FPTC showed specific binding in vitro, but not in vivo. Based on the logP value and its ability to block [125I]ICYP binding to C6 cells, FPTC may be a lead to suitable cerebral β-AR ligands.

KW - Click chemistry

KW - [(18) F]FPTC

KW - beta-AR

KW - BETA-2-ADRENERGIC RECEPTORS

KW - P-GLYCOPROTEIN

KW - BRAIN

KW - BINDING

KW - ANTAGONIST

KW - EXPRESSION

KW - CARAZOLOL

KW - DRUGS

KW - RATS

U2 - 10.1016/j.nucmedbio.2013.10.011

DO - 10.1016/j.nucmedbio.2013.10.011

M3 - Article

VL - 41

SP - 203

EP - 209

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 2

ER -

ID: 2333595