PMID:17935289
| Citation |
Chang, YT, Cheng, CM, Su, YZ, Lee, WT, Hsu, JS, Liu, GC, Cheng, TL and Wang, YM Synthesis and characterization of a new bioactivated paramagnetic gadolinium(III) complex [Gd(DOTA-FPG)(H2O)] for tracing gene expression. Bioconjug. Chem. 18:1716-27 |
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| 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. |
| Links |
PubMed Online version:10.1021/bc070019s |
| Keywords |
Animals; Cell Line, Tumor; Cell Survival/drug effects; Chelating Agents/chemical synthesis; Chelating Agents/chemistry; Chelating Agents/pharmacology; Chromatography, Liquid; Gadolinium; Gene Expression Profiling/methods; Humans; Ligands; Magnetic Resonance Imaging; Mass Spectrometry; Mice; Molecular Structure; Organometallic Compounds/chemical synthesis; Organometallic Compounds/chemistry; Organometallic Compounds/toxicity; Protein Binding; Serum Albumin/chemistry; Time Factors; Water/chemistry; beta-Galactosidase/metabolism |
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