Imaging Immune activation by FDG PET/CT after systemic cancer vaccination therapy

Ziel/Aim Immune intervention by vaccination strategies bears the potential of new and innovative treatment concepts for malignant diseases. Thus, vaccination therapies are increasingly investigated in clinical trials. In an ongoing phase I/II multicenter trial (Lipo-MERIT, NCT02410733) safety and tolerability of a new RNA-lipoplex vaccine against non-mutated melanoma associated antigens (NY-ESO-1, tyrosinase, MAGE-A3 and TPTE) are currently investigated in Stage III and IV malignant melanoma patients. To measure tumor response FDG PET/CT was offered to patients in one of the participating centers. In those patients, we now analyzed FDG uptake as a marker of in vivo immune activation and derived a temporal relationship to the time point of vaccination.

Methodik/Methods For seven patients participating in the Lipo-MERIT trial between November 2017 and July 2019 PET/CT scans were available both for baseline and during the period of active vaccination. FDG uptake in spleen was measured by obtaining mean standard uptake value from a spherical volume of interest placed in the center of the spleen. Additionally, signs of immune activation within the bone marrow were analyzed visually.

Ergebnisse/Results Mean spleen FDG uptake (SUV) at baseline was 2.0 and increased to 2.6 during vaccination (p=0.06). If taken into account the temporal relationship to the application of a particular vaccination cycle the spleen uptake was highest 4-6 h after vaccination (+73 %) compared to the later time points 20-24 h (+ 16 %). At time points between 6 and 8 days after a vaccination cycle a slight decrease of spleen uptake was measured (−10 %). Bone marrow uptake - possibly reflecting immune activation within the bone marrow - was heterogeneous without clear changes during the vaccination period compared to base line scans.

Schlussfolgerungen/Conclusions Changes in glucose metabolism in the spleen as measured by FDG PET/CT can be attributed to self-adjuvanting immune activation caused by systemic RNA-lipoplex cancer immunotherapy.