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Open Access 01-12-2018 | Original research

In vivo imaging of the immune response upon systemic RNA cancer vaccination by FDG-PET

Authors: Stefanie Pektor, Lina Hilscher, Kerstin C. Walzer, Isabelle Miederer, Nicole Bausbacher, Carmen Loquai, Mathias Schreckenberger, Ugur Sahin, Mustafa Diken, Matthias Miederer

Published in: EJNMMI Research | Issue 1/2018

Abstract

Background

[¹⁸F]Fluoro-2-deoxy-2-d-glucose positron emission tomography (FDG-PET) is commonly used in the clinic for diagnosis of cancer and for follow-up of therapy outcome. Additional to the well-established value in tumor imaging, it bears potential to depict immune processes in modern immunotherapies. T cells enhance their glucose consumption upon activation and are crucial effectors for the success of such novel therapies. In this study, we analyzed the T cell immunity in spleen after antigen-specific stimulation of T cells via highly innovative RNA-based vaccines using FDG-PET/MRI. For this purpose, we employed systemic administration of RNA-lipoplexes encoding the endogenous antigen of Moloney murine leukemia virus (gp70) which have been previously shown to induce potent innate as well as adaptive immune mechanisms for cancer immunotherapy. Feasibility of clinical imaging of increased splenic FDG uptake was demonstrated in a melanoma patient participating in a clinical phase 1 trial of a tetravalent RNA-lipoplex cancer vaccine.

Results

We observed exclusive increase of glucose uptake in spleen compared to other organs thanks to liposome-mediated RNA targeting to this immune-relevant organ. In vivo and ex vivo FDG uptake analysis in the spleen of vaccinated mice correlated well with antigen-specific T cell activation. Moreover, the use of an irrelevant (antigen non-specific) RNA also resulted in enhanced FDG uptake early after vaccination through the activation of several other splenic cell populations. The glucose uptake was also dependent on the dose of RNA administered in line with the activation and frequencies of proliferating antigen-specific T cells as well as the general activation pattern of splenic cell populations.

Conclusions

Our preclinical results show rapid and transient vaccination-induced increase of FDG uptake within the spleen reflecting immune activation preceding T cell proliferation. FDG-PET/CT in patients is also capable to image this immune activation resulting in a new potential application of FDG-PET/CT to image immune processes in new immunological therapies.

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Title: In vivo imaging of the immune response upon systemic RNA cancer vaccination by FDG-PET
Authors: Stefanie Pektor
Lina Hilscher
Kerstin C. Walzer
Isabelle Miederer
Nicole Bausbacher
Carmen Loquai
Mathias Schreckenberger
Ugur Sahin
Mustafa Diken
Matthias Miederer
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2018
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-018-0435-z

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

In vivo imaging of the immune response upon systemic RNA cancer vaccination by FDG-PET

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Results

Conclusions

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