Advancing In Vivo Detection of T‑Cell Function: Development and Preclinical Evaluation of ⁸⁹Zr‑Ivuxolimab, a Human OX40 PET Tracer

Kalita M
Stanford University
July 24, 2025
J Nucl Med
https://pubmed.ncbi.nlm.nih.gov/40707142

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/40707142

Research summary

The study developed and validated ⁸⁹Zr-labeled ivuxolimab, an anti-human OX40 antibody, for PET imaging of activated T cells. In human OX40 Knockin mice, tracer accumulation correlated with T cell activation in a graft-versus-host disease (GVHD) model. Ex vivo and in vivo PET/CT analyses confirmed high specificity and functional readout of OX40 engagement.

Key outcome of the study

⁸⁹Zr‑ivuxolimab binds activated T cells in vivo, enables longitudinal imaging of OX40⁺ populations in inflammatory models, supports translational development of OX40-targeted immunotherapies

Model

Human OX40 Knockin mouse — genOway-developed, expressing human OX40 (TNFRSF4) to replace mouse OX40, allowing in vivo detection of human OX40 with ⁸⁹Zr-ivuxolimab

TARGET:
Tnfrsf4
Synonyms:
OX40, CD134, ACT35, TXGP1L, Ly-63

Keywords

Immuno-PET imaging, T cell activation, humanized immune targets, GVHD model, translational imaging biomarkers

Technical specifications

Human OX40 gene Knockin, replacement of murine Tnfrsf4 with human sequence, PET tracer (⁸⁹Zr‑ivuxolimab), GVHD-induced activation model, in vivo T cell tracking, radiolabeling and biodistribution

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genO-hOX40

The genO-hOX40 mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint OX40 in fully immunocompetent mice.

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