Non-invasive in vivo assessment of 11β-hydroxysteroid dehydrogenase type 1 activity by 19F-Magnetic Resonance Spectroscopy.

ABSTRACT: 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies tissue glucocorticoid levels and is a pharmaceutical target in diabetes and cognitive decline. Clinical translation of inhibitors is hampered by lack of in vivo pharmacodynamic biomarkers. Our goal was to monitor substrates and products of 11β-HSD1 non-invasively in liver via 19Fluorine magnetic resonance spectroscopy (19F-MRS). Interconversion of mono/poly-fluorinated substrate/product pairs was studied in Wistar rats (male, n = 6) and healthy men (n = 3) using 7T and 3T MRI scanners, respectively. Here we show that the in vitro limit of detection, as absolute fluorine content, was 0.625 μmole in blood. Mono-fluorinated steroids, dexamethasone and 11-dehydrodexamethasone, were detected in phantoms but not in vivo in human liver

SUBMITTER: Naredo-Gonzalez G 

PROVIDER: S-EPMC9523021 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature