Biodistribution of a Mitochondrial Metabolic Tracer, [¹⁸F]F-AraG, in Healthy Volunteers

Figure 1

SAMHD1 and [¹⁸F]F-AraG uptake in antigen stimulated T cells. (a) The proposed mechanism of uptake. [¹⁸F]F-AraG is transported into cells via nucleoside transporters, followed by the rate-limiting phosphorylation by mitochondrial deoxyguanosine kinase (dGK). Once triphosphorylated, [¹⁸F]F-AraG can be incorporated into mtDNA or be exported from mitochondria where SAMHD1 can dephosphorylate triphosphate providing an opportunity for the unphosphorylated [¹⁸F]F-AraG to be exported from the cell. Overall, optimal trapping of [¹⁸F]F-AraG may be achieved in cells with high mitochondrial biogenesis and low expression of SAMHD1. (b) Accumulation of [¹⁸F]F-AraG in CEM, unstimulated and antigen-stimulated T cells. Antigen-stimulated T cells show 6-fold higher uptake than the unstimulated T cells. T-ALL CEM cells served as a positive control and showed the highest accumulation of tracer. (c) Antigen-stimulated CD8 cells (red line) show higher levels of PD-1 and CD69 and lower levels of SAMHD-1 than unstimulated cells (black line).

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