title: Synthesis and characterization of a new bioactivated paramagnetic gadolinium(III) complex [Gd(DOTA-FPG)(H2O)] for tracing gene expression.
abstract: A smart contrast agent for magnetic resonance imaging (MRI) can be used to exploit an enzymatic activity specific to the tissue or disease state signified by converting an MRI-inactivated agent to an activated MRI agent. In this study, a beta-galactopyranose-containing gadolinium(III) complex [Gd(DOTA-FPG)(H 2O)] was designed, synthesized, and characterized as being potentially suitable for a bioactivated MRI contrast agent. The (17)O NMR experiments were conducted to estimate the water exchange rate k e x 298 and rotational correlation time tau R 298 . The k ex 298 value of [Gd(DOTA-FPG)(H 2O)] is similar to that of [Gd(DO3A-bz-NO 2)(H 2O)]. The rotational correlation time value of [Gd(DOTA-FPG)(H 2O)] is dramatically longer than that of [Gd(DOTA)(H 2O)] (-) Relaxometric studies show that the percentage change in the T 1 value of [Gd(DOTA-FPG)(H 2O)] decreases dramatically in the presence of beta-galactosidase and human serum albumin. The T(1) change percentage of [Gd(DOTA-FPG)(H 2O)] (60%) is significantly higher than those of Egad and gadolinium(III)-1-(4-(2-(1-(4,7,10-triscarboxymethyl-(1,4,7,10-tetraazacyclododecyl)))-ethylcarbamoyloxymethyl)-2-nitrophenyl)-beta- d-glucopyronuronate. The signal intensity of the MR image for [Gd(DOTA-FPG)(H 2O)] in the presence of human serum albumin and beta-galactosidase (2670 +/- 210) is significantly higher than that of [Gd(DOTA-FPG)(H 2O)] in the sodium phosphate buffer solution (1490 +/- 160). In addition, the MR images show a higher-intensity enhancement in CT26/beta-gal tumor with beta-galactosidase gene expression but not for the CT26 tumor without beta-galactosidase gene expression. We conclude that [Gd(DOTA-FPG)(H 2O)] is a suitable candidate for a bioactivated MRI contrast agent in tracing gene expression.
authors.affiliation: Faculty of Medicinal and Applied Chemistry, Faculty of Biomedical Science and Environmental Biology, Department of Radiology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
authors.forename: Yu-Ton
authors.initials: YT
authors.lastname: Chang
authors.forename: Chiu-Min
authors.initials: CM
authors.lastname: Cheng
authors.forename: Yu-Zheng
authors.initials: YZ
authors.lastname: Su
authors.forename: Wei-Thung
authors.initials: WT
authors.lastname: Lee
authors.forename: Jui-Sheng
authors.initials: JS
authors.lastname: Hsu
authors.forename: Gin-Chung
authors.initials: GC
authors.lastname: Liu
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Cheng
authors.forename: Yun-Ming
authors.initials: YM
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002853:Chromatography, Liquid; D005682:Gadolinium; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008024:Ligands; D008279:Magnetic Resonance Imaging; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry; D013997:Time Factors; D014867:Water / Q000737:chemistry; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D008024:Ligands; D009942:Organometallic Compounds; D012709:Serum Albumin; C525962:gadolinium 1-(2-difluoromethyl-4-(1-(1,4,7,10-triscarboxymethyl-(1,4,7,10-tetraazacyclododecyl)acetamido)phenyl)-beta-D-galactopyranose); D014867:Water; D005682:Gadolinium; D001616:beta-Galactosidase