Preliminary in vivo evaluation of a novel 99mTc-Labeled HYNIC-cys-annexin A5 as an apoptosis imaging agent

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.