TY - JOUR
T1 - Synthesis of 11C-Labeled RXR Partial Agonist 1-[(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic Acid (CBt-PMN) by Direct [11C]Carbon Dioxide Fixation via Organolithiation of Trialkyltin Precursor and PET Imaging Thereof
AU - Shibahara, Osamu
AU - Watanabe, Masaki
AU - Yamada, Shoya
AU - Akehi, Masaru
AU - Sasaki, Takanori
AU - Akahoshi, Akiya
AU - Hanada, Takahisa
AU - Hirano, Hiroyuki
AU - Nakatani, Shunsuke
AU - Nishioka, Hiromi
AU - Takeuchi, Yasuo
AU - Kakuta, Hiroki
N1 - Funding Information:
We are grateful to the Division of Instrumental Analysis, Okayama University, for the NMR and MS measurements. This work was partially supported by a subsidy to promote science and technology in prefectures where nuclear and other power plants are located (to H.K.) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, a Grant-in-Aid for the COE projects by MEXT, Japan, titled “Center of excellence for molecular and gene targeting therapies with microdose molecular imaging modalities” (to H.K.), and Takeda Science Foundation (to H.K.).
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/8/24
Y1 - 2017/8/24
N2 - The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's diseases based on reports that RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these disease in rodent models. Here, we synthesized carbon-11-labeled ([11C]1) as a tracer for positron emission tomography (PET) and used it in a PET imaging study to examine the brain uptake and biodistribution of 1. We found that 11CO2 fixation after tin-lithium exchange at -20 °C afforded [11C]1. This methodology may also be useful for synthesizing 11CO2H-PET tracer derivatives of other compounds bearing π-rich heterocyclic rings. A PET/CT imaging study of [11C]1 in mice indicated 1 is distributed to the brain and is thus a candidate for treatment of CNS diseases.
AB - The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's diseases based on reports that RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these disease in rodent models. Here, we synthesized carbon-11-labeled ([11C]1) as a tracer for positron emission tomography (PET) and used it in a PET imaging study to examine the brain uptake and biodistribution of 1. We found that 11CO2 fixation after tin-lithium exchange at -20 °C afforded [11C]1. This methodology may also be useful for synthesizing 11CO2H-PET tracer derivatives of other compounds bearing π-rich heterocyclic rings. A PET/CT imaging study of [11C]1 in mice indicated 1 is distributed to the brain and is thus a candidate for treatment of CNS diseases.
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U2 - 10.1021/acs.jmedchem.7b00817
DO - 10.1021/acs.jmedchem.7b00817
M3 - Article
C2 - 28753292
AN - SCOPUS:85028595602
VL - 60
SP - 7139
EP - 7145
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 16
ER -