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KMID : 1145520180040020073
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Journal of Radiopharmaceuticals and Molecular Probes
2018 Volume.4 No. 2 p.73 ~ p.79
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Synthesis and biological evaluation of tricarbonyl technetium labeled 2-(4-chloro)phenyl-imidazo[1,2-a]pyridine analog (99mTcCB257) as a TSPO-binding ligand
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Choi Ji-Young
Jung Jae-Ho
Song In-Ho
Moon Byung-Seok
Lee Byung-Chul
Kim Sang-Eun
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Abstract
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In our previous study, tricarbonyl 99mTc-labeled TSPO-binding ligand, named 99mTc-CB256, having positively charge (+1) was investigated but did not show promising results in in vivo environment despite of a nanomolar binding affinity for TSPO. Because the overall positively charge of 99mTc-CB256 would likely interrupt its target protein uptake, we herein designed the neutral tricarbonyl-99mTc labeled TSPO-binding ligand (99mTc-CB257, 1). 99mTc-CB257 was prepared by the facile incorporation of the [99mTc(CO)3]+ into a N-(hydroxycarbonylmethyl)2-picoly moiety in CB257. The radiochemical yield of 99mTc-CB257 after HPLC purification was 54.1 ± 2.4% (decay corrected, n = 3). The authentic Re-CB257 (2) was synthesized by using (NEt4)2[Re(CO)3Br3] in 69.0% yield. The binding affinity of 2 for TSPO was measured in leukocyte and showed approximately 280 times higher than that observed for the positively charged (+1) ligand, Re-CB256 ( K i = 0.57 ± 0.06 nM versus 159.3 ± 8.7 nM, respectively). Our results indicated that 1 can be considered potentially as a new SPECT radiotracer for TSPO-rich cancer and provides the foundation for further in vivo evaluation related with abnormal TSPOoverexpression environments
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KEYWORD
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Translocator protein (TSPO), Tricarbonyltechnetium-99m, SPECT
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