# Project 3: Elemental Microscopy for Detection of Radionuclide Distribution and Development of Cell and Tissue Phantoms

> **NIH NIH P01** · NORTHWESTERN UNIVERSITY · 2022 · $374,452

## Abstract

PROJECT 3: ABSTRACT
The overall objective of Project 3 is to link radionuclide exposure and the elemental signature left behind with
biomarkers of that exposure, be they histological, cellular or molecular in nature. Our motivation to do this stems
from the fact that radiation from internal emitters is very unevenly distributed in organs, tissues, and cells and
the fact that this remains little understood. Heterogeneity of radionuclide distribution is dependent upon a
complex set of parameters that relate to the radionuclide itself and the organism’s response to it, such as
radionuclide half-life, decay schema, activity, concentration, particle size, morphology, chemical form, and
solubility, whereas the biological response patterns are dictated by the genotype and phenotype of the cells,
tissues and organs, intake route and the organism as a whole.
Because the in vivo footprint of radionuclide exposure is multi-scale, e.g., DNA damage and cell death at the
(sub)cellular level, or chemokine/cytokine production at the cell/tissue level, it essentially means that biomarkers
of that exposure are best registered along the same multi-dimensional NANO-, MICRO- and MESO scale, which
is our goal. For example, micro-RNA expression will be registered in the context of immune cell infiltration in a
tissue, particularly macrophages. Arguably, the most compelling aspect to our project can be seen in the use of
X-ray fluorescent microscopy (XFM) as a powerful tool for radionuclide mapping, which forms the backbone to
our approach. Applying XFM technology to explore the incredibly rich resource that the Northwestern University
Radiation Animal (NURA) Archive, combined with contemporary animal models gives us the unique opportunity
to trace back the biological consequences of radionuclide exposures, and opens up the path towards biomarker,
and ultimately, to mitigator discovery. Canine and murine tissues from an enormous number of animals exposed
to a variety of radionuclides and over different times add critical mass and rigor to our study.
Collectively, our team can draw from a diverse set of expertise in nuclear medicine, cellular and molecular
biology, radiobiology, XFM, radiation protection and mitigation, normal tissue radiobiology and immunology. We
are ideally placed to carry out the proposed studies addressing the complexity of radionuclide exposure in a
comprehensive and integrated way. Our hope is to gain important insights into the biological consequences of
internal radiation emitters that are relevant to real life accidental and incidental exposure scenarios and that
cannot be modeled using conventional external beam radiation or nuclear medicine approaches. Yet, the
concepts underlying the interaction between radiation-damaged cells and tissues, danger signaling, the
engagement of immune system and the road to recovery are likely applicable in a much broader context.

## Key facts

- **NIH application ID:** 10327398
- **Project number:** 1P01AI165380-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** GAYLE E. WOLOSCHAK
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $374,452
- **Award type:** 1
- **Project period:** 2022-03-10 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327398

## Citation

> US National Institutes of Health, RePORTER application 10327398, Project 3: Elemental Microscopy for Detection of Radionuclide Distribution and Development of Cell and Tissue Phantoms (1P01AI165380-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10327398. Licensed CC0.

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