# Delineating Functional Immunity via Image-Guided PET

> **NIH NIH R37** · WAYNE STATE UNIVERSITY · 2022 · $536,875

## Abstract

Abstract
 Recent emerging tumor-targeted immunotherapy strategies are met with positive and durable outcomes
in the clinic. Yet, at least half of cancer patients remain non-responsive despite attempts to engineer their own
immune system to attack and destroy the tumor. There is an urgent need for imaging biomarkers to universally
guide immunotherapy, regardless of tumor characteristics or treatment modality. The ability to non-invasively
and quantitatively image T cell infiltration, anti-tumor activity and expression of tumor suppressors within the
tumor through positron emission tomography (PET) will expeditiously identify targets of secondary intervention
to improve outcomes. In our proposed study, we will explore 18F-labeled diabody targeting interferon- (IFN-)
to interrogate the immune surveillance-signaling axis. We hypothesize that imaging of this immune effector
molecule, a hallmark of CD8+ cytotoxic T cell (CTL) and Th1-mediated response, will better predict therapeutic
outcomes over total CD8+ or CD3+ T cell imaging alone. We will further monitor the relationship of IFN- with
the checkpoint molecules PD-1 and its ligand PD-L1 through PET in an induced anergic microenvironment.
The established and well-characterized immune competent neu (the rat homolog of HER2) transgenic and
neu+ TUBO xenograft mice will be utilized for active and passive treatment using a HER2/neu DNA vaccine
and an anti-neu monoclonal antibody, respectively. Our second aim seeks to examine the potential of our PET
radiotracers in neu+ tumor-bearing diversity outbred mice, which recapitulate genetic heterogeneity in humans.
Genetic analysis will be conducted to identify loci associated with T cell infiltration, IFN- expression and PD-
1/PD-L1 upregulation. The goal is to identify genetic markers to predict patient susceptibility to immunotherapy
and identify potential novel targets for intervention or imaging. Finally, as a progression toward clinical
application, we will evaluate the human analog of the IFN- PET tracer against tumor tissue sections via a
retrospective histopathological review. A comparative analysis of ex vivo binding of the imaging probe against
histological scores will be conducted. Positive findings will warrant clinical translation for informed application
of therapeutic strategies. Taken together, the proposed study can potentially address the critical need to
develop image-guided tools to monitor immune-facilitated treatment as prompted by landmark cancer
immunotherapy breakthroughs.

## Key facts

- **NIH application ID:** 10454880
- **Project number:** 5R37CA220482-05
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Heather Marie Gibson
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $536,875
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454880

## Citation

> US National Institutes of Health, RePORTER application 10454880, Delineating Functional Immunity via Image-Guided PET (5R37CA220482-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10454880. Licensed CC0.

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