In Vivo Veritas - 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
Standard
In Vivo Veritas - 18F-radiolabeled glycomimetics allow insights into the pharmacological fate of galectin-3 inhibitors. / Bratteby, Klas; Torkelsson, Edvard; Tampio L'Estrade, Elina; Peterson, Kristoffer; Shalgunov, Vladimir; Xiong, Mengfei; Leffler, Hakon; Zetterberg, Fredrik; Olsson, Tomas G; Gillings, Nic; Nilsson, Ulf J; Herth, Matthias M; Erlandsson, Maria.
I: Journal of Medicinal Chemistry, Bind 63, Nr. 2, 2020, s. 747-755.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
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
Y1 - 2020
N2 - Glycomimetic drugs have attracted increasing interest as unique targeting vectors or surrogates for endogenous biomolecules. However, it's 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 in 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's 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 in 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
VL - 63
SP - 747
EP - 755
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 2
ER -
ID: 232017005