# Project 2 - Molecular Imaging of ectopic calcification

> **NIH NIH P01** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $443,274

## Abstract

PROJECT 2 SUMMARY
Molecular Imaging of Ectopic Calcification. The formation of calcified, insoluble deposits is not just a
bystander or epiphenomenon, but rather plays key roles in the pathology of Age-related Macular Degeneration
(AMD) and Alzheimer's Disease (AD), and probably other diseases of aging. Calcium deposits in the eye
between the Bruch’s membrane and the retinal pigment epithelium nucleate the formation of drusen, long
associated with AMD, and in some cases predict progression to advanced disease. Moreover in AD brains,
phosphorylated Tau is observed associated with intracellular calcification in neurons. Understanding the
calcification processes in these diseases has been hampered by the limitations of existing fluorescent stains,
particularly for studying the development of calcification in the tissues of live animal models of these diseases,
especially outside the retina. While techniques like computed tomography (CT), Positron Emission
Tomography (PET), and magnetic resonance imaging (MRI) all offer good tissue penetration, they offer only
millimeter resolution at best, and modest specificity. The thrust of this Project is to develop improved
luminescent sensors that overcome the shortcomings of the existing sensors. In particular, we will develop
sensors with tunable selectivity and kinetics, altered transduction (response), and improved targetability, that
permit detection of microscopic calcification even deep in perfused tissue. These novel sensors will be
supplied to our Projects to enable them to carry out unprecedented experiments in cells, tissues, and live
animal models of AMD, AD, and other diseases. In particular, we will develop sensors to study the continuous
development of calcification in animal models of ectopic calcification diseases such as Pseudoxanthoma
Elasticum (PXE) and Generalized Arterial Calcification of Infancy (GACI), that are capable of optically
distinguishing different chemical forms of calcification. We also will develop sensors for following calcification in
cells and subcellular organelles. Our goals in this Project are not only to develop improved tools to elucidate
the calcification processes in cellular and live animal models, but also to identify and test new therapeutic
approaches. We note that other diseases exhibiting calcification phenotypes such as atherosclerosis, heart
valve disease, and breast cancer, may also benefit from these developments.

## Key facts

- **NIH application ID:** 10878730
- **Project number:** 5P01AG081167-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** RICHARD Blair THOMPSON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $443,274
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878730

## Citation

> US National Institutes of Health, RePORTER application 10878730, Project 2 - Molecular Imaging of ectopic calcification (5P01AG081167-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10878730. Licensed CC0.

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