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 Chemjournal_title
Bioorganic & medicinal chemistryauthors
Takamura Y,Shibahara O,Watanabe M,Fujihara M,Yamada S,Akehi M,Sasaki T,Hirano H,Kakuta Hdoi
10.1016/j.bmc.2019.05.045subject
Has Abstractpub_date
2019-07-15 00:00:00pages
3128-3134issue
14eissn
0968-0896issn
1464-3391pii
S0968-0896(19)30758-8journal_volume
27pub_type
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