# Granzyme B PET imaging as a marker of inflammatory bowel disease activity

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $574,276

## Abstract

Project Summary/Abstract
Inflammatory bowel disease (IBD) is a group of inflammatory disorders associated with significant morbidity
and cost to the patients and society. With the absence of a cure, therapy is directed at control of intestinal
inflammation using anti-inflammatory and immunosuppressive agents, which have been shown to vastly improve
the outcomes and reduce complications. The use of these therapies, however, should only be limited to those
with active disease due to high cost and risk of serious adverse events such as serious infections, neurologic
disorders, heart failure, and hematologic malignancies. Endoscopy is currently the preferred method of disease
activity assessment due to high correlation with clinical outcomes. However, repeated use of endoscopy is limited
by its invasiveness, difficult administration, and restricted access to small bowel. Anatomical imaging is helpful
in detection of active disease but has limited utility in early response assessment, differentiation of fibrostenotic
disease from active inflammation or prediction of disease recurrence. Molecular imaging is currently of unclear
clinical value in IBD due to suboptimal specificity and lack of correlation with clinical indices. A biomarker of
leukocyte activity may prove to be ideal marker of intestinal inflammation and predictive of response to therapy.
Such biomarker can significantly advance IBD management by identifying subclinical inflammation to prevent
disease associated complications and reducing the cost and side effects associated with ineffective treatments.
Granzyme B (GzmB) is a marker of cytotoxic lymphocyte activity which strongly correlates with disease activity
in IBD. It is secreted in the extracellular matrix by activated lymphocytes and can mount a robust inflammatory
response by processing proinflammatory cytokines. We have developed a peptide-based PET-imaging agent,
68Ga-NOTA-GZP, with high affinity and specificity for active GzmB and a favorable biodistribution for imaging
intestinal inflammation. We have shown in our preliminary data that GZP PET uptake correlates with intestinal
inflammation in mouse models and can differentiate vehicle or anti-TNF treated mice. In human tissue specimens
of active Crohn’s disease our humanized GZP (hGZP) probe strongly stained the sites of inflammation, while in
the normal subjects and quiescent disease did not. Thus, GZP PET imaging offers a unique insight into
assessment of active inflammation and early response, not currently possible using other techniques.
We propose this study to assess and optimize a novel diagnostic method for assessment of disease activity and
early treatment response in IBD. To validate the findings in mouse models for human translation, we will correlate
the ex vivo hGZP staining of human tissue specimens with conventional histopathology. Additionally, we will
optimize a point of care diagnostic assay for rapid detection of GzmB in stool samples in mouse models and
val...

## Key facts

- **NIH application ID:** 10254339
- **Project number:** 5R01DK123143-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Umar Mahmood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $574,276
- **Award type:** 5
- **Project period:** 2020-09-04 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254339

## Citation

> US National Institutes of Health, RePORTER application 10254339, Granzyme B PET imaging as a marker of inflammatory bowel disease activity (5R01DK123143-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10254339. Licensed CC0.

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