期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 18, 期 13, 页码 3794-3798出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2008.05.044
关键词
HYNIC-cys-annexin a5; technetium-99m; apoptosis imaging
A novel cys-annexin A5 with a single cysteine-residue at its concave side has been developed by site-directed mutagenesis to allow conjugation through thiol-chemistry without affecting its apoptotic cell binding properties and was derivatized with HYNIC in a 1: 1 stoichiometry. Similar to that of the 1st generation (99m)Tc-HYNIC-annexin A5, the novel (99m)Tc-HYNIC-cys-annexin A5 derivative shows in normal mice mainly renal and, to a lesser extent, hepatobiliary excretion. In murine models of hepatic apoptosis there was 257% increase in hepatic uptake of (99m)Tc-HYNIC-cys-annexin A5 as compared to normal mice. Using the novel tracer agent, acute reperfused myocardial infarction in rabbits was unequivocally delineated at 7 h post-injection by mu SPECT. The results indicate that the novel (99m)Tc-HYNIC-cys-annexin A5 shows similar apoptosis avidity as the 1st generation (99m)Tc-HYNIC-annexin A5. (c) 2008 Elsevier Ltd. All rights reserved.
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