Fluorine-18 (18F)-labeled retinoid x receptor (RXR) partial agonist whose tissue transferability is affected by other RXR ligands.

Abstract:

:Bexarotene (1), a retinoid X receptor (RXR) agonist approved for the treatment of cutaneous T cell lymphoma (CTCL), was reported to migrate into baboon brain based on findings obtained by positron emission tomography (PET) with a 11C-labeled tracer. However, co-administration of non-radioactive 1 had no effect on the distribution of [11C]1, probably due to non-specific binding of 1 as a result of its high lipophilicity. Here, we report a fluorine-18 (18F)-labeled PET tracer [18F]6 derived from RXR partial agonist CBt-PMN (2), which has lower lipophilicity and weaker RXR-binding ability than [11C]1. The concomitant administration of 1 or 2 with [18F]6 with resulted in decreased accumulation of [18F]6 in liver, together with increased brain uptake and increased accumulation in kidney and muscle, as visualized by PET. A plausible explanation of these findings is the inhibition of [18F]6 uptake into the liver by concomitantly administered 1 or 2, leading to an increase in blood concentration of [18F]6 followed by increased accumulation in other tissues.

journal_name

Bioorg Med Chem

authors

Takamura Y,Shibahara O,Watanabe M,Fujihara M,Yamada S,Akehi M,Sasaki T,Hirano H,Kakuta H

doi

10.1016/j.bmc.2019.05.045

subject

Has Abstract

pub_date

2019-07-15 00:00:00

pages

3128-3134

issue

14

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(19)30758-8

journal_volume

27

pub_type

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