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

Yuta Takamura, Osamu Shibahara, Masaki Watanabe, Michiko Fujihara, Shoya Yamada, Masaru Akehi, Takanori Sasaki, Hiroyuki Hirano, Hiroki Kakuta

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalBioorganic and Medicinal Chemistry
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Positron emission tomography
Fluorine
Positron-Emission Tomography
Tissue
Ligands
Liver
Brain
Retinoid X Receptors
Cutaneous T-Cell Lymphoma
T-cells
Papio
Muscle
Blood
Kidney
Muscles

Keywords

  • F
  • Nuclear receptors
  • PET imaging
  • Pharmacokinetics
  • Retinoids
  • RXR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Fluorine-18 (18F)-labeled retinoid x receptor (RXR) partial agonist whose tissue transferability is affected by other RXR ligands. / Takamura, Yuta; Shibahara, Osamu; Watanabe, Masaki; Fujihara, Michiko; Yamada, Shoya; Akehi, Masaru; Sasaki, Takanori; Hirano, Hiroyuki; Kakuta, Hiroki.

In: Bioorganic and Medicinal Chemistry, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Takamura, Yuta

AU - Shibahara, Osamu

AU - Watanabe, Masaki

AU - Fujihara, Michiko

AU - Yamada, Shoya

AU - Akehi, Masaru

AU - Sasaki, Takanori

AU - Hirano, Hiroyuki

AU - Kakuta, Hiroki

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