In Vivo Veritas - 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors

Klas Bratteby; Edvard Torkelsson; Elina Tampio L'Estrade; Kristoffer Peterson; Vladimir Shalgunov; Mengfei Xiong; Hakon Leffler; Fredrik Zetterberg; Tomas G Olsson; Nic Gillings; Ulf J Nilsson; Matthias M Herth; Maria Erlandsson

doi:10.1021/acs.jmedchem.9b01692

In Vivo Veritas - 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors

Klas Bratteby, Edvard Torkelsson, Elina Tampio L'Estrade, Kristoffer Peterson, Vladimir Shalgunov, Mengfei Xiong, Hakon Leffler, Fredrik Zetterberg, Tomas G Olsson, Nic Gillings, Ulf J Nilsson, Matthias M Herth, Maria Erlandsson

Endocrinology and Metabolism

6 Citationer (Scopus)

Abstract

Glycomimetic drugs have attracted increasing interest as unique targeting vectors or surrogates for endogenous biomolecules. However, it is generally difficult to determine the in vivo pharmacokinetic profile of these compounds. In this work, two galectin-3 inhibitors were radiolabeled with fluorine-18 and used as surrogate PET tracers of TD139 and GB1107. Both compounds are promising drugs for clinical applications. In vivo evaluation revealed that both surrogates strongly differed with respect to their biodistribution profile. The disaccharide (TD139 surrogate) was rapidly eliminated from blood while the monosaccharide (GB1107 surrogate) showed no sign of excretion. The data obtained allowed us to infer the different in vivo fate of TD139 and GB1107 and rationalize how different administration routes could boost efficacy. Whereas the fast excretion profile of the TD139 surrogate indicated that systemic application of disaccharides is unfavorable, the extended biological half-life of the GB1107 surrogate indicated that systemic administration is possible for monosaccharides.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
ISSN	0022-2623
DOI	https://doi.org/10.1021/acs.jmedchem.9b01692
Status	Udgivet - 23 jan. 2020

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10.1021/acs.jmedchem.9b01692

Citationsformater

Bratteby, K., Torkelsson, E., Tampio L'Estrade, E., Peterson, K., Shalgunov, V., Xiong, M., Leffler, H., Zetterberg, F., Olsson, T. G., Gillings, N., Nilsson, U. J., Herth, M. M., & Erlandsson, M. (2020). In Vivo Veritas - 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.9b01692

Bratteby, K, Torkelsson, E, Tampio L'Estrade, E, Peterson, K, Shalgunov, V, Xiong, M, Leffler, H, Zetterberg, F, Olsson, TG, Gillings, N, Nilsson, UJ, Herth, MM & Erlandsson, M 2020, 'In Vivo Veritas - 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors', Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.9b01692

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title = "In Vivo Veritas - 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors",

abstract = "Glycomimetic drugs have attracted increasing interest as unique targeting vectors or surrogates for endogenous biomolecules. However, it is generally difficult to determine the in vivo pharmacokinetic profile of these compounds. In this work, two galectin-3 inhibitors were radiolabeled with fluorine-18 and used as surrogate PET tracers of TD139 and GB1107. Both compounds are promising drugs for clinical applications. In vivo evaluation revealed that both surrogates strongly differed with respect to their biodistribution profile. The disaccharide (TD139 surrogate) was rapidly eliminated from blood while the monosaccharide (GB1107 surrogate) showed no sign of excretion. The data obtained allowed us to infer the different in vivo fate of TD139 and GB1107 and rationalize how different administration routes could boost efficacy. Whereas the fast excretion profile of the TD139 surrogate indicated that systemic application of disaccharides is unfavorable, the extended biological half-life of the GB1107 surrogate indicated that systemic administration is possible for monosaccharides.",

author = "Klas Bratteby and Edvard Torkelsson and {Tampio L'Estrade}, Elina and Kristoffer Peterson and Vladimir Shalgunov and Mengfei Xiong and Hakon Leffler and Fredrik Zetterberg and Olsson, {Tomas G} and Nic Gillings and Nilsson, {Ulf J} and Herth, {Matthias M} and Maria Erlandsson",

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doi = "10.1021/acs.jmedchem.9b01692",

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T1 - In Vivo Veritas - 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors

AU - Bratteby, Klas

AU - Torkelsson, Edvard

AU - Tampio L'Estrade, Elina

AU - Peterson, Kristoffer

AU - Shalgunov, Vladimir

AU - Xiong, Mengfei

AU - Leffler, Hakon

AU - Zetterberg, Fredrik

AU - Olsson, Tomas G

AU - Gillings, Nic

AU - Nilsson, Ulf J

AU - Herth, Matthias M

AU - Erlandsson, Maria

PY - 2020/1/23

Y1 - 2020/1/23

N2 - Glycomimetic drugs have attracted increasing interest as unique targeting vectors or surrogates for endogenous biomolecules. However, it is generally difficult to determine the in vivo pharmacokinetic profile of these compounds. In this work, two galectin-3 inhibitors were radiolabeled with fluorine-18 and used as surrogate PET tracers of TD139 and GB1107. Both compounds are promising drugs for clinical applications. In vivo evaluation revealed that both surrogates strongly differed with respect to their biodistribution profile. The disaccharide (TD139 surrogate) was rapidly eliminated from blood while the monosaccharide (GB1107 surrogate) showed no sign of excretion. The data obtained allowed us to infer the different in vivo fate of TD139 and GB1107 and rationalize how different administration routes could boost efficacy. Whereas the fast excretion profile of the TD139 surrogate indicated that systemic application of disaccharides is unfavorable, the extended biological half-life of the GB1107 surrogate indicated that systemic administration is possible for monosaccharides.

AB - Glycomimetic drugs have attracted increasing interest as unique targeting vectors or surrogates for endogenous biomolecules. However, it is generally difficult to determine the in vivo pharmacokinetic profile of these compounds. In this work, two galectin-3 inhibitors were radiolabeled with fluorine-18 and used as surrogate PET tracers of TD139 and GB1107. Both compounds are promising drugs for clinical applications. In vivo evaluation revealed that both surrogates strongly differed with respect to their biodistribution profile. The disaccharide (TD139 surrogate) was rapidly eliminated from blood while the monosaccharide (GB1107 surrogate) showed no sign of excretion. The data obtained allowed us to infer the different in vivo fate of TD139 and GB1107 and rationalize how different administration routes could boost efficacy. Whereas the fast excretion profile of the TD139 surrogate indicated that systemic application of disaccharides is unfavorable, the extended biological half-life of the GB1107 surrogate indicated that systemic administration is possible for monosaccharides.

U2 - 10.1021/acs.jmedchem.9b01692

DO - 10.1021/acs.jmedchem.9b01692

M3 - Journal article

C2 - 31846326

SN - 0022-2623

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

ER -

In Vivo Veritas - 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors

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