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.

Keywords: (18)F; Nuclear receptors; PET imaging; Pharmacokinetics; RXR; Retinoids.