Publication

[(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

Visser, A. K. D., Ramakrishnan, N. K., Willemsen, A. T. M., Di Gialleonardo, V., de Vries, E. F. J., Kema, I. P., Dierckx, R. A. J. O. & van Waarde, A., Jan-2014, In : Journal of Cerebral Blood Flow and Metabolism. 34, 1, p. 118-125 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Visser, A. K. D., Ramakrishnan, N. K., Willemsen, A. T. M., Di Gialleonardo, V., de Vries, E. F. J., Kema, I. P., ... van Waarde, A. (2014). [(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain. Journal of Cerebral Blood Flow and Metabolism, 34(1), 118-125. https://doi.org/10.1038/jcbfm.2013.171

Author

Visser, Anniek K D ; Ramakrishnan, Nisha K ; Willemsen, Antoon T M ; Di Gialleonardo, Valentina ; de Vries, Erik F J ; Kema, Ido P ; Dierckx, Rudi A J O ; van Waarde, Aren. / [(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain. In: Journal of Cerebral Blood Flow and Metabolism. 2014 ; Vol. 34, No. 1. pp. 118-125.

Harvard

Visser, AKD, Ramakrishnan, NK, Willemsen, ATM, Di Gialleonardo, V, de Vries, EFJ, Kema, IP, Dierckx, RAJO & van Waarde, A 2014, '[(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain', Journal of Cerebral Blood Flow and Metabolism, vol. 34, no. 1, pp. 118-125. https://doi.org/10.1038/jcbfm.2013.171

Standard

[(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain. / Visser, Anniek K D; Ramakrishnan, Nisha K; Willemsen, Antoon T M; Di Gialleonardo, Valentina; de Vries, Erik F J; Kema, Ido P; Dierckx, Rudi A J O; van Waarde, Aren.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 34, No. 1, 01.2014, p. 118-125.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Visser AKD, Ramakrishnan NK, Willemsen ATM, Di Gialleonardo V, de Vries EFJ, Kema IP et al. [(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain. Journal of Cerebral Blood Flow and Metabolism. 2014 Jan;34(1):118-125. https://doi.org/10.1038/jcbfm.2013.171


BibTeX

@article{1f2b263946384f238aad82a1a240bc34,
title = "[(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain",
abstract = "The PET tracer [C-11]5-hydroxytryptophan ([C-11]5-HTP), which is converted to [C-11]5-hydroxytryptamine ([C-11]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [C-11]5-HTP in rat? Male rats were scanned with [C-11]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [C-11]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [C-11]5-HTP uptake, and the k(3). This was unexpected as NSD 1015 directly inhibits the enzyme converting [C-11]5-HTP to [C-11]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [C-11]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.",
keywords = "5-Hydroxytryptophan, Animals, Aromatic-L-Amino-Acid Decarboxylases, Brain, Carbidopa, Carbon Radioisotopes, Enzyme Inhibitors, Hydrazines, Male, Models, Biological, Positron-Emission Tomography, Rats, Rats, Wistar, Sensitivity and Specificity, Serotonin, Tissue Distribution, Tryptophan",
author = "Visser, {Anniek K D} and Ramakrishnan, {Nisha K} and Willemsen, {Antoon T M} and {Di Gialleonardo}, Valentina and {de Vries}, {Erik F J} and Kema, {Ido P} and Dierckx, {Rudi A J O} and {van Waarde}, Aren",
year = "2014",
month = "1",
doi = "10.1038/jcbfm.2013.171",
language = "English",
volume = "34",
pages = "118--125",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "SAGE Publications Inc.",
number = "1",

}

RIS

TY - JOUR

T1 - [(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

AU - Visser, Anniek K D

AU - Ramakrishnan, Nisha K

AU - Willemsen, Antoon T M

AU - Di Gialleonardo, Valentina

AU - de Vries, Erik F J

AU - Kema, Ido P

AU - Dierckx, Rudi A J O

AU - van Waarde, Aren

PY - 2014/1

Y1 - 2014/1

N2 - The PET tracer [C-11]5-hydroxytryptophan ([C-11]5-HTP), which is converted to [C-11]5-hydroxytryptamine ([C-11]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [C-11]5-HTP in rat? Male rats were scanned with [C-11]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [C-11]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [C-11]5-HTP uptake, and the k(3). This was unexpected as NSD 1015 directly inhibits the enzyme converting [C-11]5-HTP to [C-11]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [C-11]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.

AB - The PET tracer [C-11]5-hydroxytryptophan ([C-11]5-HTP), which is converted to [C-11]5-hydroxytryptamine ([C-11]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [C-11]5-HTP in rat? Male rats were scanned with [C-11]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [C-11]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [C-11]5-HTP uptake, and the k(3). This was unexpected as NSD 1015 directly inhibits the enzyme converting [C-11]5-HTP to [C-11]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [C-11]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.

KW - 5-Hydroxytryptophan

KW - Animals

KW - Aromatic-L-Amino-Acid Decarboxylases

KW - Brain

KW - Carbidopa

KW - Carbon Radioisotopes

KW - Enzyme Inhibitors

KW - Hydrazines

KW - Male

KW - Models, Biological

KW - Positron-Emission Tomography

KW - Rats

KW - Rats, Wistar

KW - Sensitivity and Specificity

KW - Serotonin

KW - Tissue Distribution

KW - Tryptophan

U2 - 10.1038/jcbfm.2013.171

DO - 10.1038/jcbfm.2013.171

M3 - Article

VL - 34

SP - 118

EP - 125

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 1

ER -

ID: 14255875