# Translational imaging and nanomedicine in inflammatory atherosclerosis

> **NIH NIH P01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $679,565

## Abstract

SUMMARY
 Thrombotic complications in atherosclerosis are decisively determined by macrophage inflammation. In
preclinical disease models, atherosclerosis is substantially diminished if macrophage numbers are decreased.
Recent work from our Program Project's investigators has shown that real life stressors aggravate
atherosclerosis in mice. In patients, psychosocial stress is a well-recognized risk factor for inflammatory
diseases, including atherosclerosis (odds ratio 2.1 for myocardial infarction). Therefore, in both animal models
and human subjects, an unmet need hinders our understanding of how risk factors for ischemic events, such
as psychosocial stress or organ ischemia, accelerate atherosclerosis.
 We and others recently described that macrophage dynamics in atherosclerotic plaque depend on
recruitment (R) of monocytes from the spleen and bone marrow, but can also arise from local proliferation
(P), especially in established atherosclerosis. Thus, to understand the processes leading to increased
inflammation in atherosclerotic plaque, i.e. progression of atherosclerosis, it is essential to measure systemic
supply parameters, including monocyte production in hematopoietic tissues (spleen, bone marrow), recruitment
of cells into the plaque, and local cell proliferation. Conversely, cell death and exit (E) may decrease the
overall macrophage number in tissue.
 Currently, we lack non-invasive means of measuring macrophage recruitment, proliferation or exit
(R/P/E) in mice and patients. This is a considerable hurdle for gaining a better understanding of basic
atherosclerosis biology and for developing new therapeutic strategies targeted to immune cells. Once
identified, these pathways could be tested as new therapeutic targets. In the clinical realm, the lack of non-
invasive tools that measure R/P/E prevents us from understanding whether or not processes discovered in
basic research translate to human patients.
 In Project 2 we propose to develop, validate, and translate innovative positron emission tomography
combined with magnetic resonance imaging (PET/MRI) methods for both preclinical and clinical measurement
of plaque macrophage dynamics. In Aim 1, we will develop integrated PET/MRI to study macrophage
recruitment to lesions, macrophage proliferation, and macrophage exit by creatively combining existing
imaging agents in atherosclerotic mice subjected to real-life stressors. In Aim 2, we will generate an immune
cell-directed nanoparticle library screen and use 89Zr radiolabeling to develop new recruitment and
proliferation (R/P) imaging agents. In Aim 3, we will test clinically-viable PET/MRI protocols in atherosclerotic
rabbits and translate protocols for clinical imaging in human patients, interfacing with Project 3.

## Key facts

- **NIH application ID:** 9884812
- **Project number:** 5P01HL131478-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Willem Mulder
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $679,565
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884812

## Citation

> US National Institutes of Health, RePORTER application 9884812, Translational imaging and nanomedicine in inflammatory atherosclerosis (5P01HL131478-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9884812. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*