Refereed journal article or data article (A1)
[Ga-68]Ga-DOTA-Siglec-9 Detects Pharmacodynamic Changes of FAP-Targeted IL2 Variant Immunotherapy in B16-FAP Melanoma Mice
List of Authors: Viitanen Riikka, Virtanen Helena, Liljenbäck Heidi, Moisio Olli, Li Xiang-Guo, Nicolini Valeria, Richard Marine, Klein Christian, Nayak Tapan, Jalkanen Sirpa, Roivainen Anne
Publisher: FRONTIERS MEDIA SA
Publication year: 2022
Journal: Frontiers in Immunology
Journal name in source: FRONTIERS IN IMMUNOLOGY
Journal acronym: FRONT IMMUNOL
Article number: 901693
Volume number: 13
Number of pages: 10
ISSN: 1664-3224
DOI: http://dx.doi.org/10.3389/fimmu.2022.901693
URL: https://www.frontiersin.org/articles/10.3389/fimmu.2022.901693/full
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/175967552
Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule, which supports contact between leukocytes and inflamed endothelium. There is evidence that VAP-1 is involved in the recruitment of leukocytes to melanoma tumors. Interleukin-2 (IL-2)-based immunotherapy is an efficient therapy that promotes immune system activity against cancers but is associated with toxicity. In the present study, we evaluated the feasibility of PET/CT imaging using the radiotracer [Ga-68]Ga-DOTA-Siglec-9, which is targeted to VAP-1, to monitor pharmacodynamic effects of a novel FAP-IL2v immunocytokine (a genetically engineered variant of IL-2 fused with fibroblast activation protein) in the B16-FAP melanoma model. At 9 days after the inoculation of B16-FAP melanoma cells, mice were studied with [Ga-68]Ga-DOTA-Siglec-9 PET/CT as a baseline measurement. Immediately after baseline imaging, mice were treated with FAP-IL2v or vehicle, and treatment was repeated 3 days later. Subsequent PET/CT imaging was performed 3, 5, and 7 days after baseline imaging. In addition to in vivo PET imaging, ex vivo autoradiography, histology, and immunofluorescence staining were performed on excised tumors. B16-FAP tumors were clearly detected with [Ga-68]Ga-DOTA-Siglec-9 PET/CT during the follow-up period, without differences in tumor volume between FAP-IL2v-treated and vehicle-treated groups. Tumor-to-muscle uptake of [Ga-68]Ga-DOTA-Siglec-9 was significantly higher in the FAP-IL2v-treated group than in the vehicle-treated group 7 days after baseline imaging, and this was confirmed by tumor autoradiography analysis. FAP-IL2v treatment did not affect VAP-1 expression on the tumor vasculature. However, FAP-IL2v treatment increased the number of CD8(+) T cells and natural killer cells in tumors. The present study showed that [Ga-68]Ga-DOTA-Siglec-9 can detect B16-FAP tumors and allows monitoring of FAP-IL2v treatment.
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