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In Vivo Veritas : 18F-Radiolabeled Glycomimetics Allow Insights into the Pharmacological Fate of Galectin-3 Inhibitors

Bratteby, Klas ; Torkelsson, Edvard ; L'Estrade, Elina Tampio ; Peterson, Kristoffer LU ; Shalgunov, Vladimir ; Xiong, Mengfei ; Leffler, Hakon LU ; Zetterberg, Fredrik R. ; Olsson, Tomas G. LU and Gillings, Nic , et al. (2020) In Journal of Medicinal Chemistry 63(2). p.747-755
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medicinal Chemistry
volume
63
issue
2
pages
9 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:85078557240
  • pmid:31846326
ISSN
0022-2623
DOI
10.1021/acs.jmedchem.9b01692
language
English
LU publication?
yes
id
f8ac85d1-8335-4673-948d-a6787a760f6b
date added to LUP
2020-12-30 14:08:55
date last changed
2024-05-16 00:27:43
@article{f8ac85d1-8335-4673-948d-a6787a760f6b,
  abstract     = {{<p>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.</p>}},
  author       = {{Bratteby, Klas and Torkelsson, Edvard and L'Estrade, Elina Tampio and Peterson, Kristoffer and Shalgunov, Vladimir and Xiong, Mengfei and Leffler, Hakon and Zetterberg, Fredrik R. and Olsson, Tomas G. and Gillings, Nic and Nilsson, Ulf J. and Herth, Matthias M. and Erlandsson, Maria}},
  issn         = {{0022-2623}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{747--755}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of Medicinal Chemistry}},
  title        = {{In Vivo Veritas : <sup>18</sup>F-Radiolabeled Glycomimetics Allow Insights into the Pharmacological Fate of Galectin-3 Inhibitors}},
  url          = {{http://dx.doi.org/10.1021/acs.jmedchem.9b01692}},
  doi          = {{10.1021/acs.jmedchem.9b01692}},
  volume       = {{63}},
  year         = {{2020}},
}