# Imaging Beta Cell Function in Vivo with Zinc Responsive MRI Contrast Agents

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $405,000

## Abstract

Type II diabetes is chronic disease characterized by temporal loss of β-cell function and gradual
insulin deficiency. Despite years of intensive research into the mechanisms of β-cell functional
decline, progress in understanding the pathogenesis of diabetes has been hampered by our
inability to monitor the fate of β-cells during progression of the disease or during therapeutic
recovery. Although various molecular imaging approaches have been demonstrated in vitro,
non-invasive imaging of β-cell mass and function in vivo remains elusive. Over the past 5½
years, our lab has improved upon the original design of a responsive MRI contrast agent that
responds to release of Zn2+ ions from secretory tissues and demonstrated that release of
insulin and Zn2+ from pancreatic β-cells initiated by a bolus of glucose bolus can be imaged in
rodents and in the macaque non-human primate. The monkey imaging studies showed that
Zn2+ and insulin secretion is not uniform throughout the pancreas, consistent with known data
on the non-uniform distribution of islets throughout the pancreas. A reduction in agent Zn2+
binding affinity (by ~103) resulted in a dramatic improvement in the sensitivity for detection of
Zn2+ secretion from the pancreas in vivo. Furthermore, we have demonstrated that one can
detect “first responder islets” as “hot spots” in the tail of the pancreas by MRI using either a
low or high affinity Zn2+ sensor. In this continuation project, we will monitor first responder
islets in two well-established T2DM model, the Zucker Diabetic Fatty (ZDF) rat (obese model)
and the Goto-Kakizaki (GK) rat (non-obese model). Animals will be imaged every 2 weeks
during progression of the disease and as they respond to clinically approved T2DM drugs. The
imaging methods will be validated by independent measures of insulin content (fluorescence)
and Zn2+ content by SR-XRF. Our goal is to demonstrate that β-cell function can be monitored
in the head and tail regions of the pancrease reproducibly by MRI and that this technology will
provide new insights into β-cell function that will catalyze development of new drugs for
T2DM.

## Key facts

- **NIH application ID:** 9972898
- **Project number:** 5R01DK095416-08
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Dean Sherry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2012-09-19 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972898

## Citation

> US National Institutes of Health, RePORTER application 9972898, Imaging Beta Cell Function in Vivo with Zinc Responsive MRI Contrast Agents (5R01DK095416-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972898. Licensed CC0.

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