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

Evaluation of a 99mTc-Labeled AnnexinA5 Variant for Non-invasive SPECT Imaging of Cell Death in Liver, Spleen and Prostate

“…These findings expand the data of Fonge et al, who showed that 99m Tc-HYNIC-cys-AnxA5 can be used to demonstrate cell death in the liver of mice treated with FAS-activating antibody and myocardial infarction-reperfusion injury in rabbits (7). With regard to drug discovery, non-invasive in vivo imaging of the PS-Cys-AnxA5 interaction in liver and spleen can provide a relevant translational biomarker to measure early effects of drugs designed to intervene in diseases that affect these organ systems.…”

“…The novel recombinant hydrazinonicotinamide-cysteine-AnxA5 (HYNIC-cysAnxA5) was obtained from MosaMedix BV (Kattendijke, The Netherlands) and has been recently described by Reutelingsperger and colleagues (7). The cys-AnxA5 variant used in the present studies contains one native cysteine, which is buried within the 3D structure of the protein, as well as one engineered cysteine residue at the concave side of the protein.…”

“…In previous studies, annexin A5 (AnxA5) has been described as a molecular probe for the imaging of cell death by virtue of its selective binding to phosphatidylserine (PS) residues that are expressed on the cell membrane of apoptotic and necrotic cells (4)(5)(6). Recently, a novel AnxA5 variant has been developed by Reutelingsperger and collaborators which allows specific radio-labeling of the protein with 99m Tc at a site which is remote from the domains involved in the interaction of AnxA5 with PS (7). In principle, labeling should therefore not negatively influence the capability of AnxA5 to bind PS on target cells.…”

Single-cell imaging of retinal ganglion cell apoptosis with a cell-penetrating, activatable peptide probe in an in vivo glaucoma model

“…One strategy to assess apoptosis in vivo has been through the use of probes targeting extracellular or cell membrane targets, such as the binding of reporter-labeled annexin V to phosphatidylserine exposed on the outer leaflet of the plasma membrane of apoptotic cells (10)(11)(12)(13). This strategy has been used to identify apoptotic RGCs in vivo (10,(14)(15)(16).…”

Site-specific labeling of ‘second generation’ annexin V with 99mTc(CO)3 for improved imaging of apoptosis in vivo

“…22,23 Recently our group has developed a novel second generation AnxV derivative with a single cysteine residue at its concave site. 24 This cys-AnxV allows site-specific conjugation of different radiometal binding ligands via sulfide formation at the cysteine residue through thiol chemistry. In this way, the introduced chelator is located at a well defined position outside the binding region of the protein, thus not affecting its binding properties.…”