Figure 5.

Key concepts in cell labeling. (A) Labeling efficiency (LE) depends on the radiotracer, cell type, and labeling conditions. A high labeling efficiency is preferable, however lower labeling efficiencies are acceptable if the subsequent retention of radioactivity by the cells is sufficiently high for the desired imaging period. To compensate for low LE, labeling can be performed with a higher starting activity to achieve the desired activity in the subject to be imaged. However, higher starting activities may pose additional costs and risks to staff involved in radiolabeling. (B) Retention of activity by labeled cells. High retention of activity within the labeled cells over the desired imaging period is essential to obtain meaningful images, even if labeling efficiencies are lower. Low retention of radioactivity by labeled cells can lead to less specific images as the localization of the radionuclide becomes decoupled from that of the cells of interest. (C) Cellular effects of radiolabeling. Radionuclides can damage cellular components directly (e.g., DNA strand breaks caused by Auger electrons or positrons) and indirectly (via water radiolysis and ROS generation). In response to ionizing radiation, cells activation endogenous repair mechanisms. Depending on the extent and nature of the damage, these repair mechanisms can salvage cells, partially repair the cells leaving them incompletely functional, or they can be overwhelmed, leading to rapid cell death. Depending on the nature of the radiation, neighboring nonlabeled cells can also be affected.