# Engineered antibody fragments for PET imaging of immunotherapeutic targets in gliomas

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $528,929

## Abstract

PROJECT SUMMARY/ABSTRACT
There are no effective non-invasive diagnostic imaging approaches to accurately stratify and monitor
immunotherapy in adults and children with glioma. PET imaging, utilizing radiolabeled antibody fragments,
minibodies (Mb), or diabodies (Db), stably chelated to radiometals, is a promising option for the safe and effective
direct quantification of cell surface markers in glioma patients that reflect dynamic immunological processes that
bear directly on immunotherapeutic effectiveness. However, development of PET for molecular imaging of
markers to guide immunotherapy is in its nascent stage. The long-term goal of this application is to translate
effective antibody fragment-based radiotracers for non-invasive diagnostic imaging before and during
immunotherapy to meaningfully impact clinical decision making for patients on immunotherapies. The overall
objective of this application is to validate radiotracer compositions for unique situations in monitoring
immunotherapies in patient-relevant murine glioma models. The rationale for the proposed research is that non-
invasive diagnostic imaging with radiotracers quantifying an important immune target, activated T-cells, and
immunosuppressive cells to prevent and shorten the duration of ineffective therapies. The central hypothesis is
that radiolabeled CD11b, EphA2, and CD69, antibody-based PET tracers can effectively guide immunotherapies
for malignant gliomas. In Aim 1, CD11b will be quantified in glioma models by PET with Cu-64-labeled anti-
CD11b Mb/Db to quantify immunosuppressive tumor-associated myeloid cells (TAMC) before and during TAMC-
targeted immunotherapies. In Aim 2 preclinical PET will be employed to quantify EphA2 expression levels in
gliomas. EphA2, a highly relevant clinical immunotherapy target, will serve as a “proof of principle” antigen, and
provide a base to develop comprehensive antigen-PET strategies. Standard uptake values (SUV) of Cu-64-
labeled anti-EphA2 Mb/Db will be used to quantify EphA2 levels on glioma cells in syngeneic orthotopic models
with a range of EphA2 levels and identify glioma-bearing mice that will respond to immunotherapies. In Aim 3,
responses to glioma immunotherapy will be assessed by CD69 PET with Cu-64-labeled anti-CD69 Mb/Db to
quantify T-cell activation and predict survival rates of glioma-bearing mice following T-cell-mediated
immunotherapies. The use of robust imaging probe chemistry, adult and pediatric murine glioma models, and
immunotherapy approaches, will validate novel human/mouse cross-reactive Mb/Db for their translational
capacity. If successful, this proposal will radically change the way gliomas are stratified and monitored on
immunotherapy trials, using real-time molecular PET imaging to determine which subjects to enroll and when to
stop or continue therapy. Outcomes from this research will greatly improve response rates to immunotherapy
while reducing unnecessary treatment-related side effects, ineffective and...

## Key facts

- **NIH application ID:** 10459345
- **Project number:** 5R01CA244520-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Wilson Barry Edwards
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $528,929
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459345

## Citation

> US National Institutes of Health, RePORTER application 10459345, Engineered antibody fragments for PET imaging of immunotherapeutic targets in gliomas (5R01CA244520-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10459345. Licensed CC0.

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