Noninvasive Immuno-PET Imaging of CD8+ T Cell Behavior in Influenza A Virus-Infected Mice

Abstract

Immuno-positron emission tomography (immuno-PET) is a noninvasive imaging method that enables tracking of immune cells in living animals. We used a nanobody that recognizes mouse CD8α and labeled it with 89Zr to image mouse CD8+ T cells in the course of an infection with influenza A virus (IAV). The CD8+ signal showed a strong increase in the mediastinal lymph node (MLN) and thymus as early as 4 days post-infection (dpi), and as early as 6 dpi in the lungs. Over the course of the infection, CD8+ T cells were at first distributed diffusely throughout the lungs and then accumulated more selectively in specific regions of the lungs. These distributions correlated with morbidity as mice reached the peak of weight loss over this interval. CD8+ T cells obtained from control or IAV-infected mice showed a difference in their distribution and migration when comparing their fate upon labeling ex vivo with 89Zr-labeled anti-CD8α nanobody and transfer into infected versus control animals. CD8+ T cells from infected mice, upon transfer, appear to be trained to persist in the lungs, even of uninfected mice. Immuno-PET imaging thus allows noninvasive, dynamic monitoring of the immune response to infectious agents in living animals.

Single-Domain Antibody Theranostics on the Horizon

“…89 Zr-VHH-X118-PEG 20 , an sdAb tracer that recognizes mouse CD8a, monitored the antitumor immune responses (39). The tracer also tracked immune cell distribution and infiltration in the graft-versus-host disease model (40) and in models of influenza A virus (41). In the context of immunotherapy, the tracer could depict the infiltration of CD8 1 T cells into the tumors and predict the therapeutic responses (42).…”

The war between the immune system and the tumor - using immune biomarkers as tracers

“…By labeling monoclonal antibodies with positron nuclides, immuno-PET combines the targeting specificity of antibodies with the high sensitivity of PET. This approach provides information on tumor immune responses across focal areas, treatment stages, and tumor progression directly by monitoring immune biomarkers such as CTLA-4, PD-1/L1, HER2, and MHC molecules [ 146 , 147 ].…”

Selective Targeting of Nanobody-Modified Gold Nanoparticles to Distinct Cell Types

“…The use of nanobodies takes advantage of their single-domain nature, their typically high affinity and specificity for the antigen of interest, as well as their ease of manufacture and modification. − Nanobodies are derived from “heavy chain only” immunoglobulins found in all members of the camelid family (llamas, alpacas, camels, and dromedaries). In suitably modified form, nanobodies have been used as imaging agents in fluorescence applications as well as for positron emission tomography (PET). − …”