Biodistribution of 99mTc-HYNIC-lactadherin in mice--a potential tracer for visualizing apoptosis in vivo.

Introduction: The aim of this study was to establish a radio synthesis of (99m)Tc-HYNIC-lactadherin for in vivo studies and to perform biodistribution analysis studies in mice, comparing (99m)Tc-HYNIC-lactadherin to (99m)Tc-HYNIC-annexin V.

Methods: The radiochemical purity of (99m)Tc-HYNIC-lactadherin was optimized by varying the amount of SnCl(2) in the synthesis. Furthermore, the need for bovine serum albumin (BSA) as a stabilizing agent was evaluated by following the stability by radiochemical purity measurement with and without the addition of BSA.

Bovine lactadherin as a calcium-independent imaging agent of phosphatidylserine expressed on the surface of apoptotic HeLa cells.

Bovine lactadherin holds a stereo-specific affinity for phosphatidylserine (PS) membrane domains and binds at PS concentrations lower than the benchmark PS probe, annexin V. Accordingly, lactadherin has recognized PS exposure on preapoptotic immortalized leukemia cells at an earlier time point than has annexin V. In the present study, the cervical cancer cell line HeLa has been employed as a model system to compare the topographic distribution of PS with the two PS binding proteins as adherent cells enter the apoptotic program.

Lactadherin detects early phosphatidylserine exposure on immortalized leukemia cells undergoing programmed cell death.

Background: Phosphatidylserine (PS) appears on the outer membrane leaflet of cells undergoing programmed cell death and marks those cells for clearance by macrophages. Macrophages secrete lactadherin, a PS-binding protein, which tethers apoptotic cells to macrophage integrins.

Methods: We utilized fluorescein-labeled lactadherin together with the benchmark PS Probe, annexin V, to detect PS exposure by flow cytometry and confocal microscopy.