Single-Cell Radiotracer Allocation via Immunomagnetic Sorting to Disentangle PET Signals at Cellular Resolution

With great interest, our independent groups of scientists located in Korea and Germany recognized the use of a very similar methodologic approach to quantify the uptake of radioactive glucose (¹⁸F-FDG) at the cellular level. The focus of our investigations was to disentangle microglial ¹⁸F-FDG uptake. To do so, CD11b immunomagnetic cell sorting was applied to isolate microglia cells after in vivo ¹⁸F-FDG injection, to allow simple quantification via a γ-counter. Importantly, this technique reveals a snapshot of cellular glucose uptake in living mice at the time of injection since ¹⁸F-FDG is trapped by hexokinase phosphorylation without a further opportunity to be metabolized. Both studies indicated high ¹⁸F-FDG uptake of single CD11b-positive microglia cells and a significant increase in microglial ¹⁸F-FDG uptake when this cell type is activated in the presence of amyloid pathology. Furthermore, another study noticed that immunomagnetic cell sorting after tracer injection facilitated determination of high ¹⁸F-FDG uptake in myeloid cells in a range of tumor models. Here, we aim to discuss the rationale for single-cell radiotracer allocation via immunomagnetic cell sorting (scRadiotracing) by providing examples of promising applications of this innovative technology in neuroscience, oncology, and radiochemistry.