• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.2
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• pp.73-79
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• 2018

In our previous study, tricarbonyl $^{99m}Tc$-labeled TSPO-binding ligand, named $^{99m}Tc$-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 $^{99m}Tc$-CB256 would likely interrupt its target protein uptake, we herein designed the neutral tricarbonyl-$^{99m}Tc$ labeled TSPO-binding ligand ($^{99m}Tc$-CB257, 1). $^{99m}Tc$-CB257 was prepared by the facile incorporation of the $[^{99m}Tc(CO)_3]^+$ into a N-(hydroxycarbonylmethyl)-2-picoly moiety in CB257. The radiochemical yield of $^{99m}Tc$-CB257 after HPLC purification was $54.1{\pm}2.4%$ (decay corrected, n = 3). The authentic Re-CB257 (2) was synthesized by using $(NEt_4)_2[Re(CO)_3Br_3]$ 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 ($K_i=0.57{\pm}0.06nM$ versus $159.3{\pm}8.7nM$, 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 TSPO-overexpression environments.