Gadolinium-based Contrast Agent Synthesis

Lactobionic acid, ethylenediamine, gadolinium chloride hexahydrate, trifluoroacetic acid(TFA), N, N-dicyclohexylcarbodiimide (DCC), N-hydroxysuccinimide (NHS), Chelex ®100 (100~ 200 mesh), 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and xylenol orange disodium salt were purchased from Sigma Aldrich (St. Louis, MO, USA). Tri-tert-butyl 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetate (tri BOC-DOTA) was purchased from Tokyo Chemical Industry Corporation (Tokyo, Japan). N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and hydrochloric acid (35–37%) were purchased from Junsei Chemical Co. Ltd. (Tokyo, Japan). Ether and acetone were purchased from Samchun Pure chemical Co. Ltd. (South Korea). Dimethyl sulfoxide-d6 (DMSO-d6) and deuterium oxide(D2O) were purchased from Cambridge Isotope Laboratories (Andover, MA, USA). Gadobutrol (Gadovist) was acquired from Bayer (Leverkusen, Germany). Chang cell (human epithelial liver cells) and HCT 116 cell (human colon carcinoma) were acquired from the American Type Culture Collection (ATCC CCL 13, USA).