# [18F]4FN PET Imaging of Innate Immunity Activation During Immunotherapy-Induced Adverse Events

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2022 · $526,490

## Abstract

ABSTRACT
 While monoclonal antibodies inhibiting immune checkpoints (ICI) and CAR T-cell therapies have
dramatically changed the therapeutic options for many cancer patients, up to 60% of patients will experience
immune-related adverse events (irAE) depending on the tumor type and immunotherapy. Thus, many patients
treated with immunotherapy will not see long term benefit and therefore only suffer potential side effects (and
possibly hyper progression), and the importance of predicting and managing immunotherapy-related adverse
events has already been identified as a critical gap in knowledge and clinical practice. Significantly, a common
molecular node of integration between the various inflammatory mechanisms of irAE, particularly in the subacute
setting, focuses on spurious activation of the innate immune system. Recently, we reported the synthesis and
validation of 4-[18F]fluoro-1-naphthol ([18F]4FN), a novel redox-tuned radiopharmaceutical for the selective
imaging of high energy oxygen and nitrogen radical species (RONS) by PET/CT. [18F]4FN provides a convenient
reagent for rapid, quantitative whole-body imaging to identify and monitor inflammatory foci generated by NADPH
oxidase-2 (NOX2) and myeloperoxidase (MPO) of the innate immune system and multi-organ inflammation,
including immunotherapy-mediated irAE. Monitoring irAE by PET imaging is the long-term clinical imaging goal
of our line of investigation. Near-term, we propose to investigate the role of activated innate immunity in vivo by
combined molecular imaging and multiplexed analysis of tissues in mechanism-based pre-clinical murine models
of irAE for which we can enhance our understanding of the activation dynamics of innate immunity and gain
signals of efficacy.

## Key facts

- **NIH application ID:** 10501365
- **Project number:** 1R01CA273130-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Sattva S Neelapu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $526,490
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501365

## Citation

> US National Institutes of Health, RePORTER application 10501365, [18F]4FN PET Imaging of Innate Immunity Activation During Immunotherapy-Induced Adverse Events (1R01CA273130-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10501365. Licensed CC0.

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