[Objective] Retinoid X receptor (RXR) agonists have been studied for the treatment of brain diseases such as Parkinson's disease.1,2 So far, we have found that RXR partial agonist CBt-PMN (1)3 translocates into mouse brain by positron emission tomography (PET) using [11C]1.4 To predict brain translocation of [10B]borono-L-phenylalanine (L-BPA, 2) for boron neutron complementary therapy (BNCT), 18F-L-BPA (3) is used.5,6 From this point of view, we got interested in comparison between 1 and F-containing CBt-PMN (F-CBt-PMN, 4). [Results] First, after synthesizing 4, its in vitro and in vivo features were compared with those of 1. The F-introduction resulted in an increase in polarity and in a decrease in the binding affinity and transactivation toward RXRα. Furthermore, comparing pharmacokinetic behaviors between the two, although similarities were observed, perfect accordance was not observed. This result was similar to the comparison between [11C]1 and [18F]4. Bexarotene (5), clinically-used RXR agonist for the treatment of cutaneous T cell lymphoma, was developed to 11C-containg PET tracer [11C]5. However, [11C]5 resulted in no competition with non-radiolebelled-5.7 We hypothesized that [18F]4, whose RXR binding ability is lower than those of 1 or 5, would be competed with 1 or 5. Interestingly, contrary to our expectation, co-administration of 1 or 5 increased the accumulation of [18F]4 in the brain, whereas decreased in the liver. These interesting results suggesting the presence of a transporter or regulating system which control absorption or excretion of RXR ligands may be based on the use of more polar and weaker PET tracer toward RXR.

F-containing retinoid X receptor (RXR) partial agonist F-CBt-PMN whose tissue transferability is affected by coadministration of another RXR ligand

2019 Fall National Meeting

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