Radiolabeling and in vivo evaluation of [11C]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT7 receptor

Elina T. L’Estrade; Ida N. Petersen; Mengfei Xiong; Adam S. Hogendorf; Agata Hogendorf; Jesper L. Kristensen; Andreas Kjær; Andrzej J. Bojarski; Maria Erlandsson; Tomas Ohlsson; Gitte M. Knudsen; Matthias M. Herth

doi:10.1007/s10967-019-06687-3

Radiolabeling and in vivo evaluation of [¹¹C]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT₇ receptor

Elina T. L’Estrade, Ida N. Petersen, Mengfei Xiong, Adam S. Hogendorf, Agata Hogendorf, Jesper L. Kristensen, Andreas Kjær, Andrzej J. Bojarski, Maria Erlandsson, Tomas Ohlsson, Gitte M. Knudsen, Matthias M. Herth^*

^*Corresponding author for this work

Abstract

AGH-44 is described as a selective low-basicity serotonin 7 receptor (5-HT₇R) agonist. In this paper, we evaluate if AGH-44 can act as a lead structure to develop a 5-HT₇R selective positron emission tomography (PET) tracer. ¹¹C-labeling of AGH-44 succeeded in a two-step, one-pot procedure in good yields. Subsequent PET studies showed that [¹¹C]AGH-44 displays low blood–brain-barrier passage in Long–Evans rats. Moreover, [¹¹C]AGH-44 brain accumulation showed to be independent on permeability glycoprotein (P-gp) efflux inhibition. Results from biodistribution and metabolism studies could neither explain the observed low brain uptake. As such, we believe that this scaffold is not an optimal starting point to develop a 5-HT₇R selective PET tracer.

Original language	English
Journal	Journal of Radioanalytical and Nuclear Chemistry
Volume	322
Issue number	2
Pages (from-to)	847-851
Number of pages	5
ISSN	0236-5731
DOIs	https://doi.org/10.1007/s10967-019-06687-3
Publication status	Published - 1 Nov 2019

Keywords

5-HT
AGH-44
Carbon-11
PET

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L’Estrade, E. T., Petersen, I. N., Xiong, M., Hogendorf, A. S., Hogendorf, A., Kristensen, J. L., Kjær, A., Bojarski, A. J., Erlandsson, M., Ohlsson, T., Knudsen, G. M., & Herth, M. M. (2019). Radiolabeling and in vivo evaluation of [¹¹C]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT₇ receptor. Journal of Radioanalytical and Nuclear Chemistry, 322(2), 847-851. https://doi.org/10.1007/s10967-019-06687-3

Radiolabeling and in vivo evaluation of [¹¹C]AGH-44 : a potential lead structure to develop a positron emission tomography radioligand for the 5-HT₇ receptor. / L’Estrade, Elina T.; Petersen, Ida N.; Xiong, Mengfei et al.

In: Journal of Radioanalytical and Nuclear Chemistry, Vol. 322, No. 2, 01.11.2019, p. 847-851.

Research output: Contribution to journal › Journal article › Research › peer-review

L’Estrade, ET, Petersen, IN, Xiong, M, Hogendorf, AS, Hogendorf, A, Kristensen, JL , Kjær, A, Bojarski, AJ, Erlandsson, M, Ohlsson, T, Knudsen, GM & Herth, MM 2019, 'Radiolabeling and in vivo evaluation of [¹¹C]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT₇ receptor', Journal of Radioanalytical and Nuclear Chemistry, vol. 322, no. 2, pp. 847-851. https://doi.org/10.1007/s10967-019-06687-3

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title = "Radiolabeling and in vivo evaluation of [11C]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT7 receptor",

abstract = "AGH-44 is described as a selective low-basicity serotonin 7 receptor (5-HT7R) agonist. In this paper, we evaluate if AGH-44 can act as a lead structure to develop a 5-HT7R selective positron emission tomography (PET) tracer. 11C-labeling of AGH-44 succeeded in a two-step, one-pot procedure in good yields. Subsequent PET studies showed that [11C]AGH-44 displays low blood–brain-barrier passage in Long–Evans rats. Moreover, [11C]AGH-44 brain accumulation showed to be independent on permeability glycoprotein (P-gp) efflux inhibition. Results from biodistribution and metabolism studies could neither explain the observed low brain uptake. As such, we believe that this scaffold is not an optimal starting point to develop a 5-HT7R selective PET tracer.",

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doi = "10.1007/s10967-019-06687-3",

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AU - Petersen, Ida N.

AU - Xiong, Mengfei

AU - Hogendorf, Adam S.

AU - Hogendorf, Agata

AU - Kristensen, Jesper L.

AU - Kjær, Andreas

AU - Bojarski, Andrzej J.

AU - Erlandsson, Maria

AU - Ohlsson, Tomas

AU - Knudsen, Gitte M.

AU - Herth, Matthias M.

PY - 2019/11/1

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N2 - AGH-44 is described as a selective low-basicity serotonin 7 receptor (5-HT7R) agonist. In this paper, we evaluate if AGH-44 can act as a lead structure to develop a 5-HT7R selective positron emission tomography (PET) tracer. 11C-labeling of AGH-44 succeeded in a two-step, one-pot procedure in good yields. Subsequent PET studies showed that [11C]AGH-44 displays low blood–brain-barrier passage in Long–Evans rats. Moreover, [11C]AGH-44 brain accumulation showed to be independent on permeability glycoprotein (P-gp) efflux inhibition. Results from biodistribution and metabolism studies could neither explain the observed low brain uptake. As such, we believe that this scaffold is not an optimal starting point to develop a 5-HT7R selective PET tracer.

AB - AGH-44 is described as a selective low-basicity serotonin 7 receptor (5-HT7R) agonist. In this paper, we evaluate if AGH-44 can act as a lead structure to develop a 5-HT7R selective positron emission tomography (PET) tracer. 11C-labeling of AGH-44 succeeded in a two-step, one-pot procedure in good yields. Subsequent PET studies showed that [11C]AGH-44 displays low blood–brain-barrier passage in Long–Evans rats. Moreover, [11C]AGH-44 brain accumulation showed to be independent on permeability glycoprotein (P-gp) efflux inhibition. Results from biodistribution and metabolism studies could neither explain the observed low brain uptake. As such, we believe that this scaffold is not an optimal starting point to develop a 5-HT7R selective PET tracer.

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Radiolabeling and in vivo evaluation of [¹¹C]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT₇ receptor

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