Toll like receptor mediated immune stimulation can be visualized in vivo by [¹⁸F]FDG-PET

Introduction: High uptake of [¹⁸F]-2-fluorodeoxyglucose ([¹⁸F]FDG) by inflammatory cells is a frequent cause of false positive results in [¹⁸F]FDG-positron-emission tomography (PET) for cancer diagnostics. Similar to cancer cells, immune cells undergo significant increases in glucose utilization following activation, e.g., in infectious diseases or after vaccination during cancer therapy. The aim of this study was to quantify certain immune effects in vitro and in vivo by [¹⁸F]FDG-PET after stimulation with TLR ligands and specific antibodies.

Methods: In vivo [¹⁸F]FDG-PET/magnetic resonance imaging (MRI) and biodistribution was performed with C57BL/6 mice immunized with CpG or LPS. Cellular [¹⁸F]FDG-uptake assays were performed with B cells and T cells or with whole spleen cells after stimulation with CpG, LPS and anti-CD3/CD28. In vitro and in vivo activation of B and T cells was examined by concomitant FACS analysis to correlate immune cell activation with the strength of [¹⁸F]FDG accumulation.

Results: We could show that TLR mediated activation of B cells increases [¹⁸F]FDG uptake, and that B cells show faster kinetics and greater effect than T cells stimulated by the CD3/CD28 pathway. In the whole spleen cell population the [¹⁸F]FDG signal was triggered mainly by the activation of B cells, corresponding closely to expression of typical stimulation markers. This finding could also been seen in vivo in [¹⁸F]FDG-PET/MRI, where the spleen was clearly visible after TLR stimulation and B cells showed upregulation of CD80 and CD86.

Conclusion: In vivo TLR stimulation can be visualized by increased [¹⁸F]FDG uptake in lymphoid organs. The signal generated in the spleen after immunization might be mainly attributed to the activation of B cells within.

Advances in knowledge and implications for patient care: Knowledge of the composition of cells that take up [¹⁸F]FDG during vaccination or in response to therapy may improve successful treatment of cancer patients in the future.