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KMID : 1145520190050020089
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Journal of Radiopharmaceuticals and Molecular Probes
2019 Volume.5 No. 2 p.89 ~ p.100
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Effect of PEG chain additive on 6,8-dichloro-2-phenylimidazo[1,2-a]pyridineacetamide (CB185) as a TSPO-binding ligand
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Lee Won-Chang
Lee Sang-Hee
Denora Nunzio
Laquintana Valentino
Lee Byung-Chul
Kim Sang-Eun
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Abstract
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In our previous studies, we developed a 18F-labeled TSPO-binding ligand, named [18F]CB251, which has beenproved to be a promising TSPO-binding PET radiotracer for the detection and monitoring of TSPO expressionin pathological diseases. (Ki = 0.27 nM for TSPO, 1.96% ID/g of tumor uptake at 1h post-injection) Basedon these results, we utilized 6,8-dichloro-2-phenylimidazo[1,2-a]pyridineacetamide analogs, CB185 (1) as atargeting moiety for the selective delivery of probes and anticancer molecules to TSPO-overexpressed tissues.
In this study, we designed CB185 derivatives contains different PEG chains (n = 1, 3 and 5) and fluorescencedye (Cy5) to identify the necessary space between a TSPO-binding ligand and an anticancer agent. ThreeCB185 derivatives (11a-c) which contains Cy5 and PEG chain, were synthesized and the effect of PEG additiveon their TSPO-binding affinities were evaluated using in vitro assays. The binding affinity for compounds 11a-cwas lower than that of PK11195 (Ki = 3.2 nM), but still characterized by nanomolar binding affinity for TSPO(Ki = 46.5 nM for 11a, 51.0 nM for 11b, and 388.5 nM for 11c). These results showed that the conjugates arecharacterized by a moderate binding affinity toward TSPO except for compound 11c, which PEG chain consistof five PEG monomers. Our finding might add useful information to decide the appropriate PET chain length fordeveloping new TSPO-targeting drug carriers.
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KEYWORD
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Translocator protein 18 kDa (TSPO), PEG Chain, Fluorescence dye (Cy5), Drug carrier
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