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 99mTc–HYNIC-annexin A5, the novel 99mTc–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 99mTc–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 μSPECT. The results indicate that the novel 99mTc–HYNIC-cys-annexin A5 shows similar apoptosis avidity as the 1st generation 99mTc–HYNIC-annexin A5.

Graphical abstractThe study describes the preliminary evaluation of technetium-99m-labeled novel ‘site-specific’ HYNIC-cys-annexin A5 as an apoptosis imaging radiotracer in animal models of hepatic apoptosis and acute myocardial infarction.Figure optionsDownload full-size imageDownload as PowerPoint slide