Positron emission tomography imaging with ⁸⁹ Zr-labeled anti-CD8 cys-diabody reveals CD8 ⁺ cell infiltration during oncolytic virus therapy in a glioma murine model.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

CD8 Antigens/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Glioma/*therapy ; Oncolytic Virotherapy/*methods; Animals ; CD8 Antigens/antagonists & inhibitors ; CD8 Antigens/isolation & purification ; CD8-Positive T-Lymphocytes/virology ; Cell Line, Tumor ; Disease Models, Animal ; Glioma/diagnostic imaging ; Glioma/immunology ; Glioma/virology ; Humans ; Mice ; Radioisotopes/pharmacology ; Simplexvirus/genetics ; Tomography, X-Ray Computed ; Zirconium/pharmacology

Determination of treatment response to immunotherapy in glioblastoma multiforme (GBM) is a process which can take months. Detection of CD8 ⁺ T cell recruitment to the tumor with a noninvasive imaging modality such as positron emission tomography (PET) may allow for tumor characterization and early evaluation of therapeutic response to immunotherapy. In this study, we utilized ⁸⁹ Zr-labeled anti-CD8 cys-diabody-PET to provide proof-of-concept to detect CD8 ⁺ T cell immune response to oncolytic herpes simplex virus (oHSV) M002 immunotherapy in a syngeneic GBM model. Immunocompetent mice (n = 16) were implanted intracranially with GSC005 GBM tumors, and treated with intratumoral injection of oHSV M002 or saline control. An additional non-tumor bearing cohort (n = 4) receiving oHSV M002 treatment was also evaluated. Mice were injected with ⁸⁹ Zr-labeled anti-CD8 cys-diabody seven days post oHSV administration and imaged with a preclinical PET scanner. Standardized uptake value (SUV) was quantified. Ex vivo tissue analyses included autoradiography and immunohistochemistry. PET imaging showed significantly higher SUV in tumors which had been treated with M002 compared to those without M002 treatment (p = 0.0207) and the non-tumor bearing M002 treated group (p = 0.0021). Accumulation in target areas, especially the spleen, was significantly reduced by blocking with the non-labeled diabody (p < 0.001). Radioactive probe accumulation in brains was consistent with CD8 ⁺ cell trafficking patterns after oHSV treatment. This PET imaging strategy could aid in distinguishing responders from non-responders during immunotherapy of GBM.
(© 2021. The Author(s).)

Erratum in: Sci Rep. 2021 Oct 8;11(1):20450. (PMID: 34625579)

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R01 AI148711 United States AI NIAID NIH HHS; R01 CA240582 United States CA NCI NIH HHS; UL1 TR001417 United States TR NCATS NIH HHS; P20 CA151129 United States CA NCI NIH HHS; T32 NS048039 United States NS NINDS NIH HHS; P30 CA013148 United States CA NCI NIH HHS

0 (CD8 Antigens)
0 (Radioisotopes)
C6V6S92N3C (Zirconium)
NTM296JU95 (Zirconium-89)

Date Created: 20210729 Date Completed: 20211101 Latest Revision: 20231107

20231107

PMC8319402

10.1038/s41598-021-94887-x

34321569