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Updated: Jan 23, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Fluorine-18 (18F)-labeled retinoid x receptor (RXR) partial agonist whose tissue transferability is affected by other
Yuta Takamura1, Osamu Shibahara1, Masaki Watanabe1
1Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-Naka, Kita-Ku, Okayama 700-8530, Japan.
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.
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